Proximal Tubule Glutamine Synthetase Expression is Necessary for the Normal Response to Dietary Protein Restriction.
Abstract Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and ¬decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of NH4+ and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increa...
Source: Am J Physiol Renal P... - March 22, 2017 Category: Urology & Nephrology Authors: Lee HW, Osis G, Handlogten ME, Verlander JW, Weiner ID Tags: Am J Physiol Renal Physiol Source Type: research

An Intracellular Matrix Metalloproteinase-2 Isoform Induces Tubular Regulated Necrosis: Implications for Acute Kidney Injury.
Abstract Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with pre-existing CKD. Oxidative stress is a common theme in models of AKI induced by ischemia/reperfusion (I/R) injury. We recently characterized an intracellular isoform of matrix metalloproteinase-2 (MMP-2) induced by oxidative stress-mediated activation of an alternate promoter in the first intron of the MMP-2 gene. This generates an N-terminal truncated MMP-2 isoform (NTT-MMP-2) that is intracellular and associated with mitochondria. The NTT-MMP-2 isoform...
Source: Am J Physiol Renal P... - March 22, 2017 Category: Urology & Nephrology Authors: Ceron CS, Baligand C, Joshi SK, Wanga S, Cowley PM, Walker JP, Song SH, Mahimkar R, Baker AJ, Raffai RL, Wang ZJ, Lovett DH Tags: Am J Physiol Renal Physiol Source Type: research

Hypoxia inducible factor-1 α activation improves renal oxygenation and mitochondrial function in early chronic kidney disease.
In conclusion, we report significant impairment of renal oxygenation and mitochondrial function at the early stages of CKD and demonstrate the beneficial role of HIF-1α activation on renal function and metabolism. PMID: 28331062 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 22, 2017 Category: Urology & Nephrology Authors: Thomas JL, Pham H, Li Y, Hall E, Perkins GA, Ali SS, Patel HH, Singh P Tags: Am J Physiol Renal Physiol Source Type: research

MicroRNA-148b regulates megalin expression and is associated with receptor downregulation in mice with unilateral ureteral obstruction.
Abstract Megalin is a multiligand, endocytic receptor important for the normal, proximal tubule reabsorption of filtered proteins, hormones, enzymes, essential nutrients, and nephrotoxins. Megalin dysfunction has been associated with acute as well as chronic kidney diseases. Tubular proteinuria has been observed following unilateral ureteral obstruction (UUO) suggesting megalin dysfunction; however, the pathophysiological mechanism has not been resolved. In order to identify potential regulators of megalin expression, we examined renal microRNAs (miRNAs) expression and observed an upregulation of microRNA-148b (mi...
Source: Am J Physiol Renal P... - March 22, 2017 Category: Urology & Nephrology Authors: Wen L, Andersen PK, Husum DM, Norregaard R, Zhao Z, Liu Z, Birn H Tags: Am J Physiol Renal Physiol Source Type: research

Maternal Separation Diminishes Alpha-Adrenergic Receptors Density and Function in Renal Vasculature from male Wistar Kyoto rats.
Abstract Adult rats exposed to maternal separation (MatSep) are normotensive but display lower glomerular filtration rate and increased renal neuroadrenergic drive. The aim of this study was to determine the renal alpha-adrenergic receptor density and the renal vascular responsiveness to adrenergic stimulation in male rats exposed to MatSep. In addition, baroreflex sensitivity was assessed to determine a component of neural control of the vasculature. Using tissue collected from 4-month-old MatSep and control rats, alpha 1-adrenergic receptors (α1-ARs) were measured in renal cortex and isolated renal vascula...
Source: Am J Physiol Renal P... - March 22, 2017 Category: Urology & Nephrology Authors: Loria AS, Osborn JL Tags: Am J Physiol Renal Physiol Source Type: research

Urothelial proliferation and regeneration after spinal cord injury.
Abstract The basal, intermediate, and superficial cell layers of the urothelium undergo rapid and complete recovery following acute injury; however, the effects of chronic injury on urothelial regeneration have not been well defined. To address this discrepancy, we employed a mouse model to explore urothelial changes in response to spinal cord injury (SCI), a condition characterized by life-long bladder dysfunction. One-day post SCI there was a focal loss of umbrella cells, which are large cells that populate the superficial cell layer and normally express uroplakins (UPKs) and KRT20, but not KRT5, KRT14, or TP63....
Source: Am J Physiol Renal P... - March 22, 2017 Category: Urology & Nephrology Authors: Kullmann FA, Clayton DR, Ruiz WG, Wolf-Johnson A, Gauthier C, Kanai AJ, Birder LA, Apodaca G Tags: Am J Physiol Renal Physiol Source Type: research

Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor- β1.
Ketamine-induced bladder fibrosis involves epithelial-to-mesenchymal transition mediated by transforming growth factor-β1. Am J Physiol Renal Physiol. 2017 Mar 22;:ajprenal.00686.2016 Authors: Wang J, Chen Y, Gu D, Zhang G, Chen J, Zhao J, Wu P Abstract Bladder wall fibrosis is a major complication of ketamine-induced cystitis (KC), but the underlying pathogenesis is poorly understood. The aim of the present study was to elucidate the mechanism of ketamine-induced fibrosis in association with epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor-β1 (TGF-β1). ...
Source: Am J Physiol Renal P... - March 22, 2017 Category: Urology & Nephrology Authors: Wang J, Chen Y, Gu D, Zhang G, Chen J, Zhao J, Wu P Tags: Am J Physiol Renal Physiol Source Type: research

Corrigendum.
Authors: PMID: 28279975 [PubMed - in process] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - March 1, 2017 Category: Urology & Nephrology Tags: Am J Physiol Renal Physiol Source Type: research

Accumulation of worn-out GBM material substantially contributes to mesangial matrix expansion in diabetic nephropathy.
öne HJ Abstract Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of diabetic nephropathy (DN) generally considered to emerge from different sites of overproduction; GBM components from podocytes and mesangial matrix from mesangial cells. Re-evaluation of 918 biopsies with DN revealed strong evidence that these mechanisms are connected to each other, wherein excess GBM components fail to undergo degradation and are deposited in the mesangium. These data do not exclude that also mesangial cells synthesize components that contribute to the accumulation of m...
Source: Am J Physiol Renal P... - February 22, 2017 Category: Urology & Nephrology Authors: Kriz W, Löwen J, Federico G, van den Born J, Gröne E, Gröne HJ Tags: Am J Physiol Renal Physiol Source Type: research

Inhibiting aerobic glycolysis suppresses renal interstitial fibroblasts activation and renal fibrosis.
In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and provide the treatment with aerobic glycolysis inhibitors as a potential anti-fibrotic strategy. PMID: 28228400 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 22, 2017 Category: Urology & Nephrology Authors: Ding H, Jiang L, Xu J, Bai F, Zhou Y, Yuan Q, Luo J, Zen K, Yang J Tags: Am J Physiol Renal Physiol Source Type: research

Wolf-Hirschhorn syndrome candidate 1-like 1 epigenetically regulates nephrin gene expression.
In conclusion, our results demonstrate that WHSC1L1-L acts as a histone methyltransferase in podocytes and regulates nephrin gene expression, which may in turn contribute to the integrity of the slit diaphragm of the glomerular filtration barrier. PMID: 28228401 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 22, 2017 Category: Urology & Nephrology Authors: Ito Y, Katayama K, Nishibori Y, Akimoto Y, Kudo A, Kurayama R, Hada I, Takahashi S, Kimura T, Fukutomi T, Katada T, Suehiro J, Beltcheva O, Tryggvason K, Yan K Tags: Am J Physiol Renal Physiol Source Type: research

Aliskiren Increases Aquaporin-2 Expression and Attenuates Lithium-induced Nephrogenic Diabetes Insipidus.
In conclusion, the direct renin inhibitor aliskiren upregulates AQP2 protein expression in inner medullary collecting duct principal cells and prevents lithium-induced nephrogenic diabetes insipidus (NDI) likely via cAMP-PKA pathways. PMID: 28228402 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 22, 2017 Category: Urology & Nephrology Authors: Lin Y, Zhang T, Feng P, Qiu M, Liu Q, Li S, Zheng P, Kong Y, Levi M, Li C, Wang W Tags: Am J Physiol Renal Physiol Source Type: research

Antenatal Betamethasone Attenuates the Angiotensin-(1-7)/Mas Receptor/Nitric Oxide Axis in Isolated Proximal Tubule Cells.
Abstract We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na(+)) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to Ang-(1-7). The present study determined the Na(+) uptake and nitric oxide (NO) response to low dose Ang-(1-7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as % of basal uptake or area under the curve (AUC) for Na(+) or % of control for NO. Male Beta RPTC exhibited greater Na(+) uptake than male vehicl...
Source: Am J Physiol Renal P... - February 22, 2017 Category: Urology & Nephrology Authors: Su Y, Bi J, Pulgar VM, Chappell MC, Rose JC Tags: Am J Physiol Renal Physiol Source Type: research

Endothelial colony forming cells ameliorate endothelial dysfunction via secreted factors following ischemia-reperfusion injury.
Abstract Damage to endothelial cells contributes to acute kidney injury (AKI) by leading to impaired perfusion. Endothelial colony-forming cells (ECFCs) are endothelial precursor cells with high proliferative capacity, pro-angiogenic activity, and in vivo vessel forming potential. We hypothesized that ECFCs may ameliorate the degree of AKI and/or promote repair of the renal vasculature following ischemia/reperfusion (I/R). Rat pulmonary microvascular ECs (PMVEC) with high proliferative potential were compared with pulmonary artery ECs (PAEC) with low proliferative potential in rats subjected to renal I/R. PMVEC ad...
Source: Am J Physiol Renal P... - February 22, 2017 Category: Urology & Nephrology Authors: Collett JA, Mehrotra P, Crone A, Shelley WC, Yoder MC, Basile DP Tags: Am J Physiol Renal Physiol Source Type: research

Inhibition of ROMK blocks macula densa tubuloglomerular feedback yet causes renal vasoconstriction in anesthetized rats.
In conclusion, blockade of ROMK or Na+/K+/2Cl- transport inhibits TGF yet increases renal vascular resistance. The renal vasoconstriction was independent of volume depletion, blood pressure, TGF or PPT. PMID: 28228405 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 22, 2017 Category: Urology & Nephrology Authors: Araujo M, Welch WJ, Zhou X, Sullivan K, Walsh S, Pasternak A, Wilcox CS Tags: Am J Physiol Renal Physiol Source Type: research

Renal Inflammation and Injury is Associated with Lymphangiogenesis in Hypertension.
Abstract Lymphatic vessels are vital for the trafficking of immune cells from the interstitium to draining lymph nodes during inflammation. Hypertension is associated with renal infiltration of activated immune cells and inflammation, however it is unknown how renal lymphatic vessels change in hypertension. We hypothesized that renal macrophage infiltration and inflammation would cause increased lymphatic vessel density in hypertensive rats. Spontaneously hypertensive rats (SHR) that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased renal lymphatic vessel density and macrophages at ...
Source: Am J Physiol Renal P... - February 22, 2017 Category: Urology & Nephrology Authors: Kneedler SC, Phillips LE, Hudson KR, Beckman KM, Lopez Gelston CA, Rutkowski JM, Parrish AR, Doris PA, Mitchell BM Tags: Am J Physiol Renal Physiol Source Type: research

Aquaporin-2 membrane targeting: still a conundrum.
Abstract The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis. In this brief review we assess the role of cyclic adenosine monophosphate (cAMP) and discuss the emerging concept that V2R-mediated AQP2 trafficking is cAMP-independent. PMID: 28179252 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 8, 2017 Category: Urology & Nephrology Authors: Olesen ET, Fenton RA Tags: Am J Physiol Renal Physiol Source Type: research

ENaC activity in the Cortical Collecting Duct of HK α1 H+,K+-ATPase knockout mice is uncoupled from Na+ intake.
ENaC activity in the Cortical Collecting Duct of HKα1 H+,K+-ATPase knockout mice is uncoupled from Na+ intake. Am J Physiol Renal Physiol. 2017 Feb 08;:ajprenal.00401.2016 Authors: Mironova E, Lynch IJ, Berman JM, Gumz ML, Stockand JD, Wingo CS Abstract Modulation of the epithelial Na+ channel (ENaC) activity in the collecting duct (CD) is an important mechanism for normal Na+ homeostasis. ENaC activity is inversely related to dietary Na+ intake, in part, due to inhibitory paracrine purinergic regulation. Evidence suggests that H+,K+-ATPase activity in the CD also influences Na+ excretion. We hy...
Source: Am J Physiol Renal P... - February 8, 2017 Category: Urology & Nephrology Authors: Mironova E, Lynch IJ, Berman JM, Gumz ML, Stockand JD, Wingo CS Tags: Am J Physiol Renal Physiol Source Type: research

A Mathematical Model of the Rat Kidney: K+-Induced Natriuresis.
Abstract A model of the rat nephron (Am. J. Physiol. 308:F1098, 2015) has been extended with addition of medullary vasculature. Blood vessels contain solutes from the nephron model, plus additional species from the model of Atherton et al. (Am. J. Physiol. 247:F61, 1984), representing hemoglobin buffering. In contrast to prior models of the urine concentrating mechanism, reflection coefficients for DVR are near zero. Model unknowns are initial proximal tubule pressures and flows, connecting tubule pressure, and medullary interstitial pressures and concentrations. The model predicts outer medullary (OM) interstitia...
Source: Am J Physiol Renal P... - February 8, 2017 Category: Urology & Nephrology Authors: Weinstein AM Tags: Am J Physiol Renal Physiol Source Type: research

Calcium-Channel Blockade blunts the Renal Effects of Acute Nitric Oxide Synthase Inhibition in Healthy Humans.
ey DZ Abstract AIMS: To investigate whether blockade of calcium channels (CCs) or Angiotensin II Type 1 receptors 1 (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. METHODS: Fourteen sodium replete healthy volunteers underwent 90 minute infusions of 3.0 μg.kg.min-1 NG-nitro-L-arginine methylester (L-NAME), on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg Manidipine (MANI), or 50 mg losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR, inulin), renal blood flow (RBF, p-aminohippurate), urinary sodium (UNaV) and 8-...
Source: Am J Physiol Renal P... - February 8, 2017 Category: Urology & Nephrology Authors: Montanari A, Lazzeroni D, Pelà G, Crocamo A, Lytvyn Y, Musiari L, Cabassi A, Cherney DZ Tags: Am J Physiol Renal Physiol Source Type: research

Zebrafish mesonephric renin cells are functionally conserved and comprise of two distinct morphological populations.
Abstract Zebrafish provide an excellent model in which to assess the role of the renin-angiotensin system in renal development, injury and repair. In contrast to mammals, zebrafish kidney organogenesis terminates with the mesonephros. Despite this, the basic functional structure of the nephron is conserved across vertebrates. The relevance of teleosts for studies relating to the regulation of the renin-angiotensin system was established by assessing the phenotype and functional regulation of renin-expressing cells in zebrafish. Transgenic fluorescent reporters for renin (ren), smooth muscle actin (acta2), and plat...
Source: Am J Physiol Renal P... - February 8, 2017 Category: Urology & Nephrology Authors: Rider SA, Christian HC, Mullins LJ, Howarth AR, MacRae CA, Mullins JJ Tags: Am J Physiol Renal Physiol Source Type: research

Interplay Between Renal Endothelin and Purinergic Signaling Systems.
Abstract Alterations in extracellular fluid volume regulation and sodium balance may result in the development and maintenance of salt-dependent hypertension, a major risk factor for cardiovascular disease. Numerous pathways contribute to the regulation of sodium excretion and blood pressure, including endothelin and purinergic signaling. Increasing evidence suggests a link between purinergic receptor activation and endothelin production within the renal collecting duct as a means of promoting natriuresis. A better understanding of the relationship between these two systems, especially in regard to sodium homeosta...
Source: Am J Physiol Renal P... - February 8, 2017 Category: Urology & Nephrology Authors: Gohar EY, Kasztan M, Pollock DM Tags: Am J Physiol Renal Physiol Source Type: research

Kidney-specific genetic deletion of both AMPK α-subunits causes salt and water wasting.
Kidney-specific genetic deletion of both AMPK α-subunits causes salt and water wasting. Am J Physiol Renal Physiol. 2017 Feb 01;312(2):F352-F365 Authors: Lazo-Fernández Y, Baile G, Meade P, Torcal P, Martínez L, Ibañez C, Bernal ML, Viollet B, Giménez I Abstract AMP-activated kinase (AMPK) controls cell energy homeostasis by modulating ATP synthesis and expenditure. In vitro studies have suggested AMPK may also control key elements of renal epithelial electrolyte transport but in vivo physiological confirmation is still insufficient. We studied sodium renal handling a...
Source: Am J Physiol Renal P... - February 1, 2017 Category: Urology & Nephrology Authors: Lazo-Fernández Y, Baile G, Meade P, Torcal P, Martínez L, Ibañez C, Bernal ML, Viollet B, Giménez I Tags: Am J Physiol Renal Physiol Source Type: research

Hitching a ride to renal repair.
PMID: 28153914 [PubMed - in process] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 1, 2017 Category: Urology & Nephrology Authors: Eirin A Tags: Am J Physiol Renal Physiol Source Type: research

Long- but not short-term estradiol treatment induces renal damage in midlife ovariectomized Long-Evans rats.
In conclusion, long-term E2 lowered blood pressure but exerted detrimental effects on kidney health in midlife OVX Long-Evans rats, whereas short-term E2 lowered blood pressure and reduced renal damage. These findings highlight that the duration of hormone therapy may be an important factor for renal health in aging postmenopausal women. PMID: 28153915 [PubMed - in process] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - February 1, 2017 Category: Urology & Nephrology Authors: Zimmerman MA, Hutson DD, Trimmer EH, Kashyap SN, Duong JL, Murphy B, Grissom EM, Daniel JM, Lindsey SH Tags: Am J Physiol Renal Physiol Source Type: research

Diabetes, hypertension and chronic kidney disease progression: Role of DPP4.
Abstract There is tremendous interest in the protein dipeptidyl peptidase 4 (DPP4) as a target in diabetes management and reduction of associated cardiovascular risk. The underlying reasons for this burgeoning interest are manifold. First, DPP4 inhibitor therapy in patients with Type 2 diabetes mellitus (T2DM) resulted in a reduction in proteinuria in the recently concluded "Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial Infarction 53" (SAVOR-TIMI 53) trial. Second, pharmacological as well as genetic inhibition of DPP4 has proven effec...
Source: Am J Physiol Renal P... - January 25, 2017 Category: Urology & Nephrology Authors: Nistala R, Savin V Tags: Am J Physiol Renal Physiol Source Type: research

Sleeping Beauty: Awakening Urothelium from its Slumber.
Abstract The bladder urothelium is essentially quiescent but regenerates readily upon injury. The process of urothelial regeneration harkens back to the process of urothelial development whereby urothelial stem/progenitor cells must proliferate and terminally differentiate to establish all three urothelial layers. How the urothelium regulates the level of proliferation and the timing of differentiation to ensure the precise degree of regeneration is of significant interest in the field. Without a carefully-orchestrated process, urothelial regeneration may be inadequate, thereby exposing the host to toxins or patho...
Source: Am J Physiol Renal P... - January 25, 2017 Category: Urology & Nephrology Authors: Balsara ZR, Li X Tags: Am J Physiol Renal Physiol Source Type: research

Primary cilia regulate the osmotic stress response of renal epithelial cells through TRPM3.
Abstract Primary cilia sense environmental conditions including osmolality, but whether cilia participate in osmotic response in renal epithelial cells is not known. Transient receptor potential (TRP) channels TRPV4 and TRPM3 are osmoresponsive. TRPV4 localizes to cilia in certain cell types, while renal subcellular localization of TRPM3 is not known. We hypothesized that primary cilia are required for maximal activation of the osmotic response of renal epithelial cells, and that ciliary TRPM3 and TRPV4 mediate that response. Ciliated (mIMCD-3 and 176-5) and non-ciliated (176-5∆) renal cells expressed Trpv4 and ...
Source: Am J Physiol Renal P... - January 25, 2017 Category: Urology & Nephrology Authors: Siroky BJ, Kleene NK, Kleene SJ, Varnell CD, Comer RG, Liu J, Lu L, Pachciarz NW, Bissler JJ, Dixon BP Tags: Am J Physiol Renal Physiol Source Type: research

Gremlin1 plays a key role in kidney development and renal fibrosis.
Abstract Grem1, an antagonist of bone morphogenetic proteins, plays a key role in embryogenesis. A highly specific temporospatial gradient of Grem1 and BMP signalling is critical to normal lung, kidney and limb development. Grem1 levels are increased in renal fibrotic conditions including acute kidney injury, diabetic nephropathy, chronic allograft nephropathy and immune glomerulonephritis. A small number of grem1-/- whole body knockout mice on a mixed genetic background (8 %) are viable, with a single, enlarged left kidney and grossly normal histology. Grem1-/- mice displayed mild renal dysfunction at 4 wk, which...
Source: Am J Physiol Renal P... - January 18, 2017 Category: Urology & Nephrology Authors: Church RH, Ali I, Tate M, Lavin D, Krishnakumar A, Kok HM, Goldschmeding R, Martin F, Brazil D Tags: Am J Physiol Renal Physiol Source Type: research

Mononuclear phagocyte subpopulations in the mouse kidney.
Abstract Mononuclear phagocytes are the most common cells in the kidney associated with immunity and inflammation. While the presence of these cells in the kidney has been known for decades, the study of mononuclear phagocytes in the context of kidney function and dysfunction is still at an early stage. The purpose of this review is to summarize the current knowledge regarding classification of these cell in the mouse kidney and to identify relevant questions that would further advance the field and potentially lead to new opportunities for treatment of acute kidney injury and other kidney diseases. PMID: 281...
Source: Am J Physiol Renal P... - January 18, 2017 Category: Urology & Nephrology Authors: George J, Lever JM, Agarwal A Tags: Am J Physiol Renal Physiol Source Type: research

MDM2 mediates fibroblast activation and renal tubulointerstitial fibrosis via p53-independent pathway.
Abstract It is well-recognized that Murine Double Minute gene 2 (MDM2) plays a critical role in cell proliferation and inflammatory processes during tumorigenesis. Also it is reported that MDM2 is expressed in glomeruli and involved in podocyte injury. However, whether MDM2 is implicated in renal fibrosis remains unclear. Here we investigated the role of MDM2 in tubulointerstitial fibrosis (TIF). By immunohistochemical staining and western blotting we confirmed that MDM2 is up-regulated in tubulointerstitial compartment in TIF patients and Unilateral Urethral Obstruction (UUO) mice, which mainly originates from my...
Source: Am J Physiol Renal P... - January 18, 2017 Category: Urology & Nephrology Authors: Ye C, Tang H, Zhao Z, Lei CT, You CQ, Zhang J, Gao P, He FF, Chen S, Wang Y, Zhang C, Su H Tags: Am J Physiol Renal Physiol Source Type: research

RACK1 Regulates Angiotensin II-Induced Contractions of SHR Preglomerular Vascular Smooth Muscle Cells.
Abstract The preglomerular microcirculation of spontaneously hypertensive rats (SHR) is hypersensitive to angiotensin II, and studies show that this is likely due to enhanced convergent signaling between G-protein subunits αq (Gαq; released by angiotensin II) and G-protein subunits βγ (Gβγ; released by Gi-coupled receptors) to active phospholipase C (PLC). Here we investigated the molecular basis for the enhanced convergent signaling between Gβγ and Gαq in SHR preglomerular vascular smooth muscle cells (PGVSMCs). Because receptor for activated C kinase 1 (RACK1; s...
Source: Am J Physiol Renal P... - January 18, 2017 Category: Urology & Nephrology Authors: Zhu X, Jackson EK Tags: Am J Physiol Renal Physiol Source Type: research

Chronic kidney disease promotes chronic inflammation in visceral white adipose tissue.
Abstract White adipose tissue plays an important role in the development of metabolic disturbance which is a common feature in patients with chronic kidney disease (CKD). The effect of CKD on white adipose tissue remains poorly appreciated. Here we evaluated the inflammatory potential of visceral white adipose tissue in a rat model of CKD. The results showed production of pro-inflammatory cytokines and infiltration of macrophage in the tissue were significantly increased in CKD rats than sham rats. Moreover, the primary adipocytes and stromal vascular fraction under the condition of CKD could trigger the inflammat...
Source: Am J Physiol Renal P... - January 18, 2017 Category: Urology & Nephrology Authors: Xiang DM, Song XZ, Zhou ZM, Liu Y, Dai XY, Huang XL, Hou FF, Zhou QG Tags: Am J Physiol Renal Physiol Source Type: research

A New Microscope for the Kidney: Mathematics.
Abstract N/A. PMID: 28100504 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 18, 2017 Category: Urology & Nephrology Authors: Layton AT Tags: Am J Physiol Renal Physiol Source Type: research

(5R)-5-Hydroxytriptolide ameliorates lupus nephritis in MRL/lpr mice by preventing infiltration of immune cells.
In this study, we aimed to investigate the therapeutic effects of LLDT-8 on lupus nephritis in MRL/lpr mice, a model of systemic lupus erythematosus. Compared with vehicle group, different clinical parameters were improved upon LLDT-8 treatment: prolonged life-span of mice, decreased proteinuria, downregulated blood urea nitrogen and serum creatinine, reduced glomerular IgG deposits, and ameliorated histopathology. A decreased expression of the inflammatory cytokines IFN-γ, IL-17, IL-6, TNF-α was also observed in the kidney of LLDT-8 treated MRL/lpr mice. Moreover, infiltration of T cells into kidney was mitiga...
Source: Am J Physiol Renal P... - January 18, 2017 Category: Urology & Nephrology Authors: Zhang LY, Li H, Wu YW, Cheng L, Yan YX, Yang XQ, Zhu FH, He SJ, Tang W, Zuo JP Tags: Am J Physiol Renal Physiol Source Type: research

Antioxidant treatment attenuates lactate production in diabetic nephropathy.
In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment. This demonstrates a pivotal role of oxidative stress in renal metabolic alterations occurring in early diabetes. PMID: 28069660 [PubMed - in process] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - January 1, 2017 Category: Urology & Nephrology Authors: Laustsen C, Nielsen PM, Nørlinger TS, Qi H, Pedersen UK, Bertelsen LB, Østergaard JA, Flyvbjerg A, Ardenkjær-Larsen JH, Palm F, Stødkilde-Jørgensen H Tags: Am J Physiol Renal Physiol Source Type: research

Bimodal dynamics of granular organelles in primary renin-expressing cells revealed using TIRF microscopy.
Abstract Renin is the initiator and rate-limiting factor in the renin-angiotensin blood pressure regulation system. Although renin is not exclusively produced in the kidney, in nonmurine species the synthesis and secretion of the active circulatory enzyme is confined almost exclusively to the dense core granules of juxtaglomerular (JG) cells, where prorenin is processed and stored for release via a regulated pathway. Despite its importance, the structural organization and regulation of granules within these cells is not well understood, in part due to the difficulty in culturing primary JG cells in vitro and the l...
Source: Am J Physiol Renal P... - January 1, 2017 Category: Urology & Nephrology Authors: Buckley C, Dun AR, Peter A, Bellamy C, Gross KW, Duncan RR, Mullins JJ Tags: Am J Physiol Renal Physiol Source Type: research

Endoplasmic reticulum stress inhibition limits the progression of chronic kidney disease in the Dahl salt-sensitive rat.
Abstract Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment. We assessed blood pressure and markers of CKD, including proteinuria, albumi...
Source: Am J Physiol Renal P... - January 1, 2017 Category: Urology & Nephrology Authors: Yum V, Carlisle RE, Lu C, Brimble E, Chahal J, Upagupta C, Ask K, Dickhout JG Tags: Am J Physiol Renal Physiol Source Type: research

A new mouse model of hemorrhagic shock-induced acute kidney injury.
Abstract Current animal models of hemorrhagic shock-induced acute kidney injury (HS-induced AKI) require extensive surgical procedures and constant monitoring of hemodynamic parameters. Application of these HS-induced AKI models in mice to produce consistent kidney injury is challenging. In the present study, we developed a simple and highly reproducible mouse model of HS-induced AKI by combining moderate bleeding and renal pedicle clamping, which was abbreviated as HS-AKI. HS was induced by retroorbital bleeding of 0.4 ml blood in C57BL/6 mice. Mice were left in HS stage for 30 min, followed by renal pedicle clam...
Source: Am J Physiol Renal P... - January 1, 2017 Category: Urology & Nephrology Authors: Wang L, Song J, Buggs J, Wei J, Wang S, Zhang J, Zhang G, Lu Y, Yip KP, Liu R Tags: Am J Physiol Renal Physiol Source Type: research

Insulin-Like Growth Factor Binding Protein 7 and Tissue Inhibitor of Metalloproteinases-2: Differential Expression and Secretion in Human Kidney Tubule Cells.
Abstract We have characterized the expression and secretion of the acute kidney injury biomarkers Insulin-Like Growth Factor Binding Protein 7 (IGFBP7) and Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubu...
Source: Am J Physiol Renal P... - December 21, 2016 Category: Urology & Nephrology Authors: Emlet DR, Pastor-Soler N, Marciszyn A, Wen X, Gomez H, Humphries WH, Morrisroe S, Volpe JK, Kellum JA Tags: Am J Physiol Renal Physiol Source Type: research

Involvement of ENaC in the development of salt-sensitive hypertension.
Abstract Salt-sensitive hypertension is associated with renal and vascular dysfunctions which lead to impaired fluid excretion, increased cardiac output and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron which plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions. In this mini-review we summarize recent studies investigating role...
Source: Am J Physiol Renal P... - December 21, 2016 Category: Urology & Nephrology Authors: Pavlov TS, Staruschenko A Tags: Am J Physiol Renal Physiol Source Type: research

The effects of exogenous desmopressin on a model of heat stress nephropathy in mice.
CONCLUSIONS: Our studies document both glomerular and tubulointerstitial injury and inflammation in heat stress nephropathy, and may be clinically relevant to the pathogenesis of Mesoamerican Nephropathy. Our data also suggest that vasopressin may play a role in the pathogenesis of the renal injury of heat stress nephropathy, likely via a V2-receptor dependent pathway. PMID: 28003190 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - December 21, 2016 Category: Urology & Nephrology Authors: Roncal-Jimenez CA, Milagres T, Andres-Hernando A, Kuwabara M, Jensen T, Song Z, Bjornstad P, Garcia GE, Sato Y, Sanchez-Lozada LG, Lanaspa MA, Johnson RJ Tags: Am J Physiol Renal Physiol Source Type: research

Calcineurin Inhibitor Cyclosporine A Activates Renal Na-(K)-Cl Cotransporters via Local and Systemic Mechanisms.
Abstract Calcineurin dephosphorylates NFAT transcription factors, thereby facilitating T-cell mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation, but may cause side effects including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA). An involvement of major hormones like angiotensin II or...
Source: Am J Physiol Renal P... - December 21, 2016 Category: Urology & Nephrology Authors: Blankenstein KI, Borschewski A, Labes R, Paliege A, Boldt C, McCormick JA, Ellison DH, Bader M, Bachmann S, Mutig K Tags: Am J Physiol Renal Physiol Source Type: research

A Perspective on Chronic Kidney Disease Progression.
Abstract Chronic kidney disease (CKD) will progress to end stage without treatment, but the decline of renal function may not be linear. Compared to GFR and proteinuria, new surrogate markers, such as KIM-1, NGAL, apoA-IV, and soluble urokinase receptor (suPAR), may allow potential intervention and treatment in the earlier stages of CKD, which could be useful for clinical trials. New omic-based technologies reveal potential new genomic and epigenomic mechanisms which appear different from those causing the initial disease. Various clinical studies also suggest that acute kidney injury (AKI) is a major risk for pro...
Source: Am J Physiol Renal P... - December 14, 2016 Category: Urology & Nephrology Authors: Zhong J, Yang H, Fogo AB Tags: Am J Physiol Renal Physiol Source Type: research

MicroRNA-30e Targets BNIP3L to Protect against Aldosterone-induced Podocyte Apoptosis and Mitochondrial Dysfunction.
Abstract MicroRNAs (miRNAs) are essential for the maintenance of podocyte homeostasis. Emerging evidence demonstrated a protective role of miRNA-30a, a member of miR-30 family in podocyte injury. However, the role of other members of miR-30 family in podocyte injury is unclear. The present study was undertaken to investigate the contribution of miR-30e in the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. Following Aldo treatment, miR-30e was dose-and time-dependently reduced. Notably, overexpression of miR-30e remarkably attenuated Aldo-induced apoptosis in pod...
Source: Am J Physiol Renal P... - December 14, 2016 Category: Urology & Nephrology Authors: Guo Y, Deng X, Chen S, Yang L, Ni J, Wang R, Lin J, Bai M, Jia Z, Huang S, Zhang A Tags: Am J Physiol Renal Physiol Source Type: research

From 20th Century Metabolic Wall Charts to 21st Century Systems Biology: Database of Mammalian Metabolic Enzymes.
Abstract The organization of the mammalian genome into gene subsets corresponding to specific functional classes has provided key tools for systems biology research. Here, we have created a web-accessible resource called the Mammalian Metabolic Enzyme Database (https://hpcwebapps.cit.nih.gov/ESBL/Database/MetabolicEnzymes/MetabolicEnzymeDatabase.html) keyed to the biochemical reactions represented on iconic metabolic pathway wall charts created in the previous century. Overall, we have mapped 1647 genes to these pathways, representing approximately 7 percent of the protein-coding genome. To illustrate the use of t...
Source: Am J Physiol Renal P... - December 14, 2016 Category: Urology & Nephrology Authors: Corcoran CC, Grady CR, Pisitkun T, Parulekar J, Knepper MA Tags: Am J Physiol Renal Physiol Source Type: research

Renin-Angiotensin System Transgenic Mouse Model Recapitulates Pathophysiology Similar to Human Preeclampsia with Renal Injury that may be Mediated through VEGF.
Abstract Using a transgenic cross, we evaluated features of preeclampsia, renal injury and the sFlt1/VEGF changes. Transgenic hAGT and hREN, or wild type (WT) C57Bl/6 mice were cross-bred: ♀hAGT x ♂hREN for preeclampsia (PRE) model and ♀WT x ♂WT for pregnant controls (WTP). Samples were collected for plasma VEGF, sFlt1 and urine albumin. Blood pressures (BP) were monitored by telemetry. Vascular reactivity was investigated by wire myography. Kidneys and placenta were immunostained for sFlt1 and VEGF. Eleven PRE and 9 WTP mice were compared. PRE more frequently demonstrated albuminuria, glomerular endotheli...
Source: Am J Physiol Renal P... - December 7, 2016 Category: Urology & Nephrology Authors: Denney JM, Bird CE, Gendron-Fitzpatrick A, Sampene E, Bird IM, Shah DM Tags: Am J Physiol Renal Physiol Source Type: research

Cilostazol inhibits uremic toxin-induced vascular smooth muscle cell dysfunction : role of Axl signaling.
This study aimed to identify the effect of cilostazol in VSMCs in the experimental CKD and to investigate whether the regulatory mechanism occurs through Axl signaling. We investigated the effect of P-cresol and cilostazol on Axl signaling in A7r5 rat VSMCs and the rat, human CKD models. From in vivo CKD rats and patients, aortic tissue exhibited significantly decreased Axl expression after cilostazol treatment. P-cresol increased Axl, PCNA, FAK and MMP-2 expressions, decreased caspase-3 expression, and was accompanied with increased cell viability and migration. Cilostazol significantly reversed P-cresol-induced Axl, down...
Source: Am J Physiol Renal P... - December 7, 2016 Category: Urology & Nephrology Authors: Lee CH, Hung YJ, Shieh YS, Chien CY, Hsu YJ, Lin CY, Chiang CF, Huang CL, Hsieh CH Tags: Am J Physiol Renal Physiol Source Type: research

Cellular transport of L-Arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.
In conclusion, the reduced L-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular L-arginine and the upregulated cortical tissue L-arginine may protect cortical hemodynamics in diabetes. PMID: 27927650 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - December 7, 2016 Category: Urology & Nephrology Authors: Persson P, Fasching A, Teerlink T, Hansell P, Palm F Tags: Am J Physiol Renal Physiol Source Type: research

DNA repair in ischemic acute kidney injury.
Abstract Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) leading to an induction of oxidative stress, cellular dysfunction and a loss of renal function. DNA damage, including oxidative base modifications and physical DNA strand breaks, is a consequence of renal IRI. Like many other organs in the body, a redundant and highly conserved set of endogenous repair pathways have evolved to selectively recognize the various types of cellular DNA damage and combat its negative effects on cell viability. Severe damage to the DNA, however, can trigger cell death and elimination of the injured...
Source: Am J Physiol Renal P... - December 7, 2016 Category: Urology & Nephrology Authors: Pressly JD, Park F Tags: Am J Physiol Renal Physiol Source Type: research