Ion transport in the zebrafish kidney from a human disease angle: possibilities, considerations and future perspectives.
Abstract Unique experimental advantages, such as its embryonic/larval transparency, high-throughput nature and ease of genetic modification, underpin the rapid emergence of the zebrafish (Danio rerio) as a preeminent model in biomedical research. Particularly in the field of nephrology, the zebrafish provides a promising model for studying the physiological implications of human solute transport processes along consecutive nephron segments. However, while the zebrafish might be considered a valuable model for numerous renal ion transport diseases and functional studies of many channels and transporters, not all hu...
Source: Am J Physiol Renal P... - November 16, 2016 Category: Urology & Nephrology Authors: Kersten S, Arjona FJ Tags: Am J Physiol Renal Physiol Source Type: research

DBA2J db/db mice are susceptible to early albuminuria and glomerulosclerosis that correlates with systemic insulin resistance.
rd RJ Abstract Diabetic nephropathy (DN) is the leading cause of kidney failure in the world. To understand important mechanisms underlying this condition, and to develop new therapies, good animal models are required. In mouse models of type-1 diabetes, the DBA/2J strain has been shown to be more susceptible to develop kidney disease than other common strains. We hypothesized this would also be the case in type-2 diabetes. We studied db/db and wt DBA/2J mice and compared these with the db/db BLKS/J mouse, which is currently the most widely used type-2 DN model. Mice were analyzed from age 6 to 12 weeks for system...
Source: Am J Physiol Renal P... - November 16, 2016 Category: Urology & Nephrology Authors: Østergaard MV, Pinto V, Stevenson K, Worm J, Fink LN, Coward RJ Tags: Am J Physiol Renal Physiol Source Type: research

IL-17 mediates neutrophil infiltration and renal fibrosis following recovery from ischemia reperfusion:compensatory role of Natural Killer cells in athymic rats.
Abstract T cells have been implicated in the pathogenesis of AKI as well as its progression to CKD. Previous studies suggest that Th17 cells participates during the AKI to CKD transition and inhibition of T cell activity by mycophenolate mofetil (MMF) or losartan attenuates the development of fibrosis following AKI. We hypothesized that T cell deficient rats may have reduced levels of IL-17 cytokine leading to decreased fibrosis following AKI. Renal I/R was performed on T cell deficient athymic rats (Foxn1rnu-/rnu-) and control euthymic rats (Foxn1rnu-/+) and CKD progression was hastened by unilateral nephrectomy ...
Source: Am J Physiol Renal P... - November 16, 2016 Category: Urology & Nephrology Authors: Mehrotra P, Collett JA, McKinney S, Stevens J, Ivancic CM, Basile DP Tags: Am J Physiol Renal Physiol Source Type: research

Vascular endothelium in diabetes.
VASCULAR ENDOTHELIUM IN DIABETES. Am J Physiol Renal Physiol. 2016 Nov 16;:ajprenal.00473.2016 Authors: Goligorsky MS Abstract Three decades ago a revolutionary idea ascribing to dysfunctional endothelia some manifestations of diabetes was born, the Steno hypothesis. Here I briefly outline the accomplishments made in the past 15 years to buttress this hypothesis. Those include development of novel technological platforms to examine microcirculatory beds, deeper understanding of patterns of microvascular derangement in diabetes, pathophysiology of nitric oxide synthesis and availability, nitrosative an...
Source: Am J Physiol Renal P... - November 16, 2016 Category: Urology & Nephrology Authors: Goligorsky MS Tags: Am J Physiol Renal Physiol Source Type: research

The critical role of Kr üppel-like factors in kidney disease.
The critical role of Krüppel-like factors in kidney disease. Am J Physiol Renal Physiol. 2016 Nov 16;:ajprenal.00550.2016 Authors: Mallipattu SK, Estrada CC, He JC Abstract Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation to progression of kidney fibrosis. Seventeen members of the KLF family have...
Source: Am J Physiol Renal P... - November 16, 2016 Category: Urology & Nephrology Authors: Mallipattu SK, Estrada CC, He JC Tags: Am J Physiol Renal Physiol Source Type: research

Am J Physiol Renal Physiol; +16 new citations
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2016/11/04PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - November 4, 2016 Category: Urology & Nephrology Tags: Report Source Type: research

Deletion of Protein Kinase C- ε Attenuates Mitochondrial Dysfunction and Ameliorates Ischemic Renal Injury.
This study tested whether deletion of the PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44% and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC-ε-deficient (KO) mice after ischemia. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT, but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively,...
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Nowak G, Takacsova Bakajsova D, Megyesi J Tags: Am J Physiol Renal Physiol Source Type: research

The native TRPP2-dependent channel of murine renal primary cilia.
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening monogenic renal disease. ADPKD results from mutations in either of two proteins: polycystin-1 (also known as PC1 or PKD1) or transient receptor potential cation channel, subfamily P, member 2 (TRPP2, also known as polycystin-2, PC2, or PKD2). Each of these proteins is expressed in the primary cilium that extends from many renal epithelial cells. Existing evidence suggests that the cilium can promote renal cystogenesis, while PC1 and TRPP2 counter this cystogenic effect. To better understand the function of TRPP2, we i...
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Kleene SJ, Kleene NK Tags: Am J Physiol Renal Physiol Source Type: research

Mesenchymal stem cells protect against obstruction-induced renal fibrosis by decreasing stat3 activation and stat3-dependent mmp-9 production.
MESENCHYMAL STEM CELLS PROTECT AGAINST OBSTRUCTION-INDUCED RENAL FIBROSIS BY DECREASING STAT3 ACTIVATION AND STAT3-DEPENDENT MMP-9 PRODUCTION. Am J Physiol Renal Physiol. 2016 Oct 19;:ajprenal.00311.2016 Authors: Matsui F, Babitz S, Rhee A, Hile KL, Zhang H, Meldrum KK Abstract STAT3 is a transcription factor implicated in renal fibrotic injury, but the role of STAT3 in mesenchymal stem cell (MSC)-induced renoprotection during renal fibrosis remains unknown. We hypothesized that MSCs protect against obstruction-induced renal fibrosis by downregulating STAT3 activation and STAT3-induced matrix metallop...
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Matsui F, Babitz S, Rhee A, Hile KL, Zhang H, Meldrum KK Tags: Am J Physiol Renal Physiol Source Type: research

ILK and Cytoskeletal Architecture: An Important Determinant of AQP2 Recycling and Subsequent Entry into the Exocytotic Pathway.
os S, Lu HJ Abstract Within the past decade tremendous efforts have been made to understand the mechanism behind aquaporin-2 (AQP2) water channel trafficking and recycling, in order to open a path towards effective diabetes insipidus therapeutics. A recent study has shown that Integrin-Linked Kinase (ILK) conditional-knockdown mice developed polyuria along with decreased expression of AQP2. To understand whether ILK also regulates AQP2 trafficking in kidney tubular cells, we performed in vitro analysis using LLCPK1 cells stably expressing rat AQP2 (LLC-AQP2 cells). Upon treatment of LLC-AQP2 cells with ILK inhibit...
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Mamuya FA, Cano-Peñalver JL, Li WU, Rodriguez-Puyol D, Rodríguez-Puyol M, Brown D, de Frutos S, Lu HJ Tags: Am J Physiol Renal Physiol Source Type: research

A small molecule screening to detect potential therapeutic targets in human podocytes.
CONCLUSION: We hereby identify compounds that alter PMR. The PMR assay provides a new avenue to test therapeutics for nephrotic syndrome. Positive results may reveal novel pathways in the study of glomerular diseases such as SRNS. PMID: 27760769 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Widmeier E, Tan W, Airik M, Hildebrandt F Tags: Am J Physiol Renal Physiol Source Type: research

Inflammation Drives Renal Scarring in Experimental Pyelonephritis.
Abstract Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The exte...
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Li B, Haridas B, Jackson AR, Cortado H, Mayne N, Kohnken R, Bolon B, McHugh KM, Schwaderer AL, Spencer JD, Ching CB, Hains DS, Justice SS, Partida-Sanchez S, Becknell B Tags: Am J Physiol Renal Physiol Source Type: research

Molecular mechanisms regulating aquaporin-2 in kidney collecting duct.
Abstract Kidney collecting duct is an important renal tubular segment for regulation of body water homeostasis and urine concentration. Water reabsorption in the collecting duct principal cells is controlled by vasopressin, a peptide hormone which induces the osmotic water transport across the collecting duct epithelia through regulation of water channel proteins aquaporin-2 (AQP2) and aquaporin-3 (AQP3). In particular, vasopressin induces both intracellular translocation of AQP2-bearing vesicles to the apical plasma membrane and transcription of Aqp2 gene to increase AQP2 protein abundance. The signaling pathways...
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Jung HJ, Kwon TH Tags: Am J Physiol Renal Physiol Source Type: research

Downregulation of kidney expression of protective factors by renal and systemic inflammation: role of transcription factors and epigenetic mechanisms.
tiz A Abstract Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR). Klotho has anti-aging and nephroprotective properties and decreased...
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Ruiz-Andres O, Sanchez-Niño MD, Moreno JA, Ruiz-Ortega M, Ramos AM, Sanz AB, Ortiz A Tags: Am J Physiol Renal Physiol Source Type: research

Stop that podocyte!
Abstract n/a. PMID: 27760773 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 19, 2016 Category: Urology & Nephrology Authors: Gupta V, Reiser J Tags: Am J Physiol Renal Physiol Source Type: research

Effects of Dietary Iron Intake and Chronic Kidney Disease on Fibroblast Growth Factor 23 Metabolism in Wild Type and Hepcidin Knockout Mice.
Abstract In the setting of normal kidney function, iron deficiency is associated with increased FGF23 production and cleavage, altering circulating FGF23 levels. Our objective was to determine how chronic kidney disease (CKD) and dietary iron intake affect FGF23 production and metabolism in wild type (WT) and hepcidin knockout (HKO) mice. For eight weeks, the mice were fed diets that contained adenine (to induce CKD) or no adenine (control group), with either low iron (4 ppm) or standard iron (335 ppm) concentrations. The low iron diet induced iron deficiency anemia in both the WT and HKO mice. Among the WT mice, ...
Source: Am J Physiol Renal P... - October 12, 2016 Category: Urology & Nephrology Authors: Hanudel MR, Chua K, Rappaport M, Gabayan V, Valore E, Goltzman D, Ganz T, Nemeth E, Salusky IB Tags: Am J Physiol Renal Physiol Source Type: research

Depletion of vacuolar protein sorting-associated protein 35 is associated with increased lysosomal degradation of aquaporin-2.
Abstract Carboxyl-terminus of AQP2 (AQP2c) undergoes post-translational modifications, including phosphorylation and ubiquitination, for the regulation of aquaporin-2 (AQP2) translocation and protein abundance. We aimed to identify novel proteins interacting with AQP2c. Recombinant AQP2c protein was made in E. coli BL21 (DE3) by exploiting the pET32 TrxA fusion system. Lysates of rat kidney inner medullary collecting duct (IMCD) tubule suspensions interacted with rat AQP2c bound to Ni(2+)-resin were subjected to LC-MS/MS proteomic analysis. Potential interacting proteins were identified, including vacuolar protein...
Source: Am J Physiol Renal P... - October 12, 2016 Category: Urology & Nephrology Authors: Lee MS, Choi HJ, Park EJ, Park HJ, Kwon TH Tags: Am J Physiol Renal Physiol Source Type: research

Long-term aldosterone administration increases renal Na+-Cl- cotransporter abundance in late distal convoluted tubule.
Abstract Renal Na+-Cl- cotransporter (NCC) is expressed in early distal convoluted tubule (DCT) 1 and late DCT (DCT2). NCC activity can be stimulated by aldosterone, and the mechanism is assumed to depend on the enzyme, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids that would otherwise occupy aldosterone receptors. Because 11β-HSD2 in rat may only be abundantly expressed in DCT2 cells and not in DCT1 cells, it has been speculated that aldosterone specifically stimulates NCC activity in DCT2 cells. In mice, however, it is debated if 11β-HSD2 is expressed i...
Source: Am J Physiol Renal P... - October 12, 2016 Category: Urology & Nephrology Authors: Poulsen SB, Christensen BM Tags: Am J Physiol Renal Physiol Source Type: research

The Relationship between Urinary Renin Angiotensin System Markers, Renal and Vascular Function in Adolescents with Type 1 Diabetes.
Abstract AIMS: The relationship between the renal renin-angiotensin aldosterone system (RAAS) and cardiorenal pathophysiology is unclear. Our aims were to assess (1) levels of urinary RAAS components and (2) the association between RAAS components and HbA1c, urine albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) and blood pressure in otherwise healthy adolescents with type 1 diabetes mellitus (TID) vs. healthy controls (HC). METHODS: Urinary angiotensinogen and ACE2 levels, activity of ACE and ACE2, blood pressure (BP), HbA1c, ACR and eGFR were measured in 65 HC and 194 T1D from the...
Source: Am J Physiol Renal P... - October 12, 2016 Category: Urology & Nephrology Authors: Burns KD, Lytvyn Y, Mahmud FH, Daneman D, Deda L, Dunger DB, Deanfield JE, Dalton RN, Elia Y, Har R, Van JA, Bradley TJ, Slorach C, Hui W, Xiao F, Zimpelmann J, Mertens L, Moineddin R, Reich HN, Sochett EB, Scholey JW, Cherney DZ Tags: Am J Physiol Renal Physiol Source Type: research

Protease-activated receptors in kidney disease progression.
Abstract Protease-activated receptors (PARs) are a well-known family of transmembrane G-protein-coupled receptors (GPCRs). To date, four PARs have been identified and PAR1 and PAR2 are the most abundant receptors, which were shown to be expressed in the kidney vascular and tubular cells. PAR signaling is mediated by an N-terminus tethered ligands that can be unmasked by serine protease cleavage. PARs are activated by endogenous serine proteases, such as thrombin (acts on PARs 1, 3 and 4) and trypsin (PAR2). PARs can be involved in glomerular, microvascular and inflammatory regulation of renal function in both norm...
Source: Am J Physiol Renal P... - October 12, 2016 Category: Urology & Nephrology Authors: Palygin O, Ilatovskaya DV, Staruschenko A Tags: Am J Physiol Renal Physiol Source Type: research

What we need to know about renal nerve ablation for treatment of hypertension and other states of sympathetic overactivity.
PMID: 27630063 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - September 14, 2016 Category: Urology & Nephrology Authors: Schlaich MP Tags: Am J Physiol Renal Physiol Source Type: research

MRI tools for assessment of microstructure and nephron function of the kidney.
This article reviews the novel tools to examine kidney microstructure and local function, and demonstrates the application of these methods in renal pathophysiology. PMID: 27630064 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - September 14, 2016 Category: Urology & Nephrology Authors: Xie L, Bennett KM, Liu C, Johnson GA, Zhang JL, Lee VS Tags: Am J Physiol Renal Physiol Source Type: research

Role of the Deubiquitinating Enzyme Ubiquitin-specific Protease-14 in Proteostasis in Renal Cells.
In conclusion, Usp14 controls proteasomal degradation of some misfolded proteins. In addition, a Usp14-directed inhibitor reduces cytotoxicity in the context of global protein misfolding during certain types of renal cell injury. PMID: 27630065 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - September 14, 2016 Category: Urology & Nephrology Authors: Sareen-Khanna K, Papillon J, Wing SS, Cybulsky AV Tags: Am J Physiol Renal Physiol Source Type: research

Temporal deletion of Aqp11 in mice is linked to the severity of cyst-like disease.
This study examined 1) whether postnatal deletion of Aqp11 affects PT injury and cyst formation, 2) the temporal role of Aqp11 deletion on cyst development, and 3) the nature of apparent cysts. Tamoxifen-inducible Aqp11(-/-) mice were generated (Ti-Aqp11(-/-)). Deletion of Aqp11 at post-natal (P) days 2, 4, 6, 8 and 12 was investigated. Deranged renal development, especially in kidney cortex, PT cell vacuolization and apparent tubular cysts developed only in mice where Aqp11 gene disruption was induced until P8. Aqp11 gene deletion from P12 onwards did not result in a clear deficiency in renal development, PT injury or cys...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Rützler M, Rojek A, Damgaard MV, Andreasen A, Fenton RA, Nielsen S Tags: Am J Physiol Renal Physiol Source Type: research

Loss of endothelin B receptor function impairs sodium excretion in a time- and sex-dependent manner.
Abstract Recent studies suggested a direct link between circadian rhythms and regulation of sodium excretion. Endothelin-1 (ET-1) regulates sodium balance by promoting natriuresis through the endothelin B receptor (ETB) in response to increased salt in the diet, but the effect that the time of day has on this natriuretic response is not known. Therefore, this study was designed to test the hypothesis that ETB receptor activation contributes to the diurnal control of sodium excretion, and that sex differences contribute to this control as well. 12-hour urine collections were used to measure sodium excretion. On day...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Johnston JG, Speed JS, Jin C, Pollock DM Tags: Am J Physiol Renal Physiol Source Type: research

Functionomics of ncc mutations in gitelman syndrome using a novel mammalian cell-based activity assay.
In conclusion, we developed a mammalian cell-based assay in which NCC activity assessment together with a profiling of the mutated protein processing aids to our understanding of the pathogenic mechanism of the NCC mutations. PMID: 27582097 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Valdez-Flores MA, Vargas-Poussou R, Verkaart S, Tutakhel OA, Valdez-Ortiz A, Blanchard A, Treard C, Hoenderop JG, Bindels RJ, Jeleń S Tags: Am J Physiol Renal Physiol Source Type: research

Proteinuria causes dysfunctional autophagy in the proximal tubule.
Abstract Proteinuria is a major risk factor for chronic kidney disease progression. Furthermore, exposure of proximal tubular epithelial cells to excess albumin promotes tubular atrophy and fibrosis, key predictors of progressive organ dysfunction. However, the link between proteinuria and tubular damage is unclear. We propose that pathologic albumin exposure impairs proximal tubular autophagy, an essential process for recycling damaged organelles and toxic intracellular macromolecules. In both mouse primary proximal tubule and immortalized human kidney cells, albumin exposure decreased the number of autophagosome...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Nolin AC, Mulhern RM, Panchenko MV, Pisarek-Horowitz A, Wang Z, Shirihai OS, Borkan SC, Havasi A Tags: Am J Physiol Renal Physiol Source Type: research

Elevated PTH induces endothelial to chondrogenic transition in aortic endothelial cells.
Abstract Previous studies have shown that increased parathyroid hormone (PTH) due to secondary hyperparathyroidism in chronic kidney disease accelerates the arteriosclerotic fibrosis and calcification. Although the underlying mechanisms remain largely unknown, endothelial cells (ECs) have recently been demonstrated to participate in calcification in part by providing chondrogenic cells via the endothelial-to-mesenchymal transition (EndMT). Therefore, this study aimed to investigate whether elevated PTH could induce endothelial to chondrogenic transition in aortic ECs and to determine the possible underlying signal...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Wu M, Zhang JD, Tang RN, Crowley SD, Liu H, Lv LL, Ma KL, Liu BC Tags: Am J Physiol Renal Physiol Source Type: research

Lymphocyte specific deletion of IKK2 or NEMO mediates increase of intrarenal Th17 cells and accelerates renal damage in ischemia reperfusion injury mouse model.
In conclusion, although systemic IKK2 inhibition improved kidney function, lymphocyte-specific deletion of IKK2 or NEMO aggravated kidney injury after IRI, and in both conditions, the percentage of Th17 cells was increased. Our findings demonstrate the critical role of the NF-κB pathway in Th17 activation, which advises caution when using systemic IKK2 inhibitors in patients with kidney injury as they might impair the T cell response and aggravate renal disease. PMID: 27582100 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Guo L, Lee HH, Noriega ML, Paust HJ, Zahner G, Thaiss F Tags: Am J Physiol Renal Physiol Source Type: research

A fate mapping approach reveals the composite origin of the connecting tubule and alerts on "single-cell" specific KO model of the distal nephron.
In conclusion, these results demonstrate that the origin of different cell types in the distal nephron is not as clearly defined as originally thought. Importantly, they highlight the fact that knocking out a gene encoding for a selective functional marker in the adult life does not guarantee cell specificity during the overall kidney development. Tools allowing not only cell-specific but also time-controlled recombination will be useful in this sense. PMID: 27582101 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Trepiccione F, Soukaseum C, Iervolino A, Petrillo F, Zacchia M, Schütz G, Eladari D, Capasso G, Hadchouel J Tags: Am J Physiol Renal Physiol Source Type: research

Re-thinking Glomerular Basement Membrane Thickening in Diabetic Nephropathy--Adaptive or Pathogenic?
This article will explore the biological significance of GBM thickening in DN by reviewing what is known about the GBM's formation, its maintenance during health, and its disruption in DN. PMID: 27582102 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Marshall CB Tags: Am J Physiol Renal Physiol Source Type: research

Both CLIC4 and CLIC5A activate ERM Proteins in Glomerular Endothelium.
Abstract The chloride intracellular channel (CLIC) 5A is expressed at very high levels in renal glomeruli, in both endothelial cells (EC) and podocytes. CLIC5A stimulates Rac1- and PI[4,5]P2-dependent ERM (ezrin, radixin, moesin) activation. ERM proteins, in turn, function in lumen formation and in the development of actin-based cellular projections. In mice lacking CLIC5A, ERM phosphorylation is profoundly reduced in podocytes, but preserved in glomerular EC. Since glomerular EC also express CLIC4, we reasoned if CLIC4 activates ERM proteins like CLIC5A, then CLIC4 could compensate for the CLIC5A loss in glomerul...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Tavasoli M, Al-Momany A, Wang X, Li L, Edwards JC, Ballermann BJ Tags: Am J Physiol Renal Physiol Source Type: research

Ironing out the crosstalk between FGF23 and inflammation.
Abstract The bone-secreted hormone fibroblast growth factor 23 (FGF23) has an essential role in phosphate homeostasis by regulating expression of the kidney proximal tubule sodium-phosphate co-transporters as well as parathyroid hormone levels. Induction of FGF23 early in chronic kidney disease (CKD) helps to maintain normal phosphorous levels. However, high FGF23 levels become pathologic as kidney disease progresses and are associated with an increased risk of CKD progression, cardiovascular events, and death. The factors responsible for increasing FGF23 levels early in CKD are unknown, but recent work has propos...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: David V, Francis C, Babitt JL Tags: Am J Physiol Renal Physiol Source Type: research

Nrf2-akt interactions regulate heme oxygenase 1 expression in kidney epithelia during hypoxia and hypoxia-reoxygenation.
NRF2-AKT INTERACTIONS REGULATE HEME OXYGENASE 1 EXPRESSION IN KIDNEY EPITHELIA DURING HYPOXIA AND HYPOXIA-REOXYGENATION. Am J Physiol Renal Physiol. 2016 Aug 31;:ajprenal.00362.2016 Authors: Reddy Potteti H, Reddy Tamatam C, Marreddy R, Reddy NM, Noel S, Rabb H, Reddy SP Abstract Ischemia-reperfusion (IR)-induced kidney injury is a major clinical problem, but the underlying mechanisms remain unclear. The transcription factor Nuclear Factor, Erythroid 2-like 2 (NFE2L2 or Nrf2) is crucial for protection against oxidative stress generated by pro-oxidant insults. We have previously shown that Nrf2 deficie...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Reddy Potteti H, Reddy Tamatam C, Marreddy R, Reddy NM, Noel S, Rabb H, Reddy SP Tags: Am J Physiol Renal Physiol Source Type: research

Human Epithelial Na+ Channel Missense Variants Identified in the GenSalt Study Alter Channel Activity.
This study sought to identify functional human ENaC variants, to examine how these variants alter channel activity, and to explore whether these variants are associated with altered sensitivity of blood pressure to dietary salt. Six-hundred participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study with salt-sensitive or salt-resistant blood pressure underwent sequencing of the genes encoding ENaC subunits. Functional effects of identified variants were examined in a Xenopus oocyte expression system. Variants that increased channel activity included three in the gene encoding the α subunit (...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Ray EC, Chen J, Kelly TN, He J, Hamm LL, Gu D, Shimmin LC, Hixson JE, Rao DC, Sheng S, Kleyman TR Tags: Am J Physiol Renal Physiol Source Type: research

Extracellular Vesicles in Diagnosis and Therapy of Kidney Diseases.
Abstract Extracellular vesicles (EV) are endogenously produced, membrane-bound vesicles that contain various molecules. Depending on their size and origins, EVs are classified into apoptotic bodies, microvesicles, and exosomes. A fundamental function of EVs is to mediate intercellular communication. In kidneys, recent research has begun to suggest a role of EVs, especially exosomes, in cell-cell communication by transferring proteins, mRNAs, and microRNAs to recipient cells as nanovectors. EVs may mediate the cross-talk between various cell types within kidneys for the maintenance of tissue homeostasis. They may a...
Source: Am J Physiol Renal P... - August 31, 2016 Category: Urology & Nephrology Authors: Zhang W, Zhou X, Zhang H, Yao Q, Liu Y, Dong Z Tags: Am J Physiol Renal Physiol Source Type: research

Targeting cytokine signaling in salt-sensitive hypertension.
Abstract Activated immune cell populations contribute to hypertension in part through inciting damage to the kidney and by provoking inappropriate sodium reabsorption in the nephron. Inflammatory mediators called cytokines produced by T lymphocytes and macrophages act on specific sodium transporters in the kidney, augmenting their activity or expression, with consequent expansion of intravascular fluid volume and cardiac output. The overlapping functions of these cytokines, each of which may activate multiple receptors, present challenges in precisely targeting inflammatory signaling cascades in hypertension. More...
Source: Am J Physiol Renal P... - August 24, 2016 Category: Urology & Nephrology Authors: Crowley SD, Jeffs AD Tags: Am J Physiol Renal Physiol Source Type: research

Immunity and Inflammation in Diabetic Kidney Disease: Translating Mechanisms to Biomarkers and Treatment Targets.
This article reviews the involvement of the immune system in DKD and identifies important roles of key immune and inflammatory mediators. One of the most recently identified biomarkers is serum amyloid A (SAA), which appears to be relatively specific for DKD. Novel and evolving treatment approaches target protein kinases, transcription factors, chemokines, adhesion molecules, growth factors, advanced glycation end-products and other inflammatory molecules. This is the beginning of a new era in the understanding and treatment of DKD and we may have finally reached a tipping point in our fight against the growing burden of D...
Source: Am J Physiol Renal P... - August 24, 2016 Category: Urology & Nephrology Authors: Pichler R, Afkarian M, Dieter BP, Tuttle KR Tags: Am J Physiol Renal Physiol Source Type: research

Age dependent shifts in renal response to injury relate to altered BMP6/CTGF expression and signaling.
Abstract Age is associated with an increased prevalence of chronic kidney disease (CKD), which, through progressive tissue damage and fibrosis, ultimately leads to loss of kidney function. Although much effort is put into studying CKD development experimentally, age has rarely been taken into account. Therefore, we investigated the effect of age on the development of renal tissue damage and fibrosis in a mouse model of obstructive nephropathy (i.e. unilateral ureter obstruction; UUO). We observed that after 14 days, obstructed kidneys of old mice had more tubulointerstitial atrophic damage but less fibrosis than t...
Source: Am J Physiol Renal P... - August 24, 2016 Category: Urology & Nephrology Authors: Falke LL, Kinashi H, Dendooven A, Broekhuizen R, Stoop R, Joles JA, Nguyen TQ, Goldschmeding R Tags: Am J Physiol Renal Physiol Source Type: research

Inter-organ handling of Fibroblast Growth Factor-23 in humans.
Abstract Fibroblast Growth Factor-23 (FGF-23) accumulates in blood of patients with chronic kidney disease (CKD) and is associated both with cardiovascular complications and disease progression. However, our knowledge of the sites and mechanisms which regulate plasma FGF-23 is still incomplete. We measured plasma intact FGF-23 across the kidney, splanchnic organs and lung in eleven patients (eGFR 60 ± 6 ml/min) during elective diagnostic cardiac catheterizations. In these patients FGF-23 was removed by the kidney, with a fractional extraction (FE) of ~22%. The FE of FGF-23 across the kidney was similar to t...
Source: Am J Physiol Renal P... - August 24, 2016 Category: Urology & Nephrology Authors: Verzola D, Ansaldo F, Milanesi S, Parodi EL, Rosa GM, Sofia A, Bonanni A, Viazzi F, Balbi M, Garibotto G Tags: Am J Physiol Renal Physiol Source Type: research

Environmental hit on a genetic basis in polycystic kidney disease.
Abstract not required? PMID: 27558561 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 24, 2016 Category: Urology & Nephrology Authors: Wang S, Dong Z Tags: Am J Physiol Renal Physiol Source Type: research

The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway.
In conclusion, this study demonstrates that although direct stimulation with cAMP causes AQP2 membrane targeting, cAMP is not necessary for receptor-mediated AQP2 membrane targeting and Gs coupled receptors can also signal through an alternative pathway that increase AQP2 membrane targeting. PMID: 27558562 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 24, 2016 Category: Urology & Nephrology Authors: Olesen ET, Moeller HB, Assentoft M, MacAulay N, Fenton RA Tags: Am J Physiol Renal Physiol Source Type: research

Effect of orchiectomy and testosterone replacement on lower urinary tract function in anesthetized rats.
Abstract Lower urinary tract symptoms (LUTS), including frequency, urgency, incomplete voiding, slow stream are common in both men and women with advancing age. The most common cause for LUTS in aging men is benign prostatic hyperplasia (BPH). Some studies have also revealed an inverse association of serum testosterone levels with LUTS; however the underlying mechanisms by which gonadal hormones affect the LUT have not been clarified. In the present study, we examined the effect of orchiectomy and testosterone replacement on lower urinary tract function in adult male Sprague-Dawley rats. Six weeks after bilateral ...
Source: Am J Physiol Renal P... - August 17, 2016 Category: Urology & Nephrology Authors: Cheng CL, de Groat WC Tags: Am J Physiol Renal Physiol Source Type: research

Activation of the Metabolic Sensor AMP-Activated Protein Kinase Inhibits Aquaporin-2 Function in Kidney Principal Cells.
Abstract Aquaporin-2 (AQP2) is essential to maintain body water homeostasis. AQP2 traffics from intracellular vesicles to the apical membrane of kidney collecting duct principal cells in response to vasopressin (AVP), a hormone released with low intravascular volume, which causes decreased kidney perfusion. Decreased kidney perfusion activates AMP-activated kinase (AMPK), a metabolic sensor that inhibits the activity of several transport proteins. We hypothesized that AMPK activation also inhibits AQP2 function. These putative AMPK effects could protect interstitial ionic gradients required for urinary concentrati...
Source: Am J Physiol Renal P... - August 17, 2016 Category: Urology & Nephrology Authors: Al-Bataineh MM, Li H, Ohmi K, Gong F, Marciszyn A, Naveed S, Zhu X, Neumann D, Wu Q, Cheng L, Fenton RA, Pastor-Soler NM, Hallows KR Tags: Am J Physiol Renal Physiol Source Type: research

Catalytic Iron and Acute Kidney Injury.
Abstract Acute kidney injury (AKI) is a common and often devastating condition among hospitalized patients, and is associated with markedly increased hospital length of stay, mortality, and cost. The pathogenesis of AKI is complex, but animal models support an important role for catalytic iron in causing AKI. Catalytic iron, also known as labile iron, is a transitional pool of non-transferrin-bound iron that is readily available to participate in redox cycling. Initial findings related to catalytic iron and animal models of kidney injury have only recently been extended to human AKI. In this review, we discuss the...
Source: Am J Physiol Renal P... - August 17, 2016 Category: Urology & Nephrology Authors: Leaf DE, Swinkels DW Tags: Am J Physiol Renal Physiol Source Type: research

Physiological insights into novel therapies for nephrogenic diabetes insipidus.
Abstract Fundamental kidney physiology research can provide important insight into how the kidney works and suggest novel therapeutic opportunities to treat human diseases. This is especially true for Nephrogenic Diabetes Insipidus (NDI). Over the past decade, studies elucidating the molecular physiology and signaling pathways regulating water transport have suggested novel therapeutic possibilities. In patients with congenital NDI due to mutations in the type 2 vasopressin receptor (V2R) or acquired NDI due to lithium (or other medications), there are no functional abnormalities in the aquaporin-2 (AQP2) water ch...
Source: Am J Physiol Renal P... - August 17, 2016 Category: Urology & Nephrology Authors: Sands JM, Klein JD Tags: Am J Physiol Renal Physiol Source Type: research

Quantification of intact plasma AGT consisting of oxidized and reduced conformations using a modified ELISA.
Abstract The pleiotropic actions of the renin-angiotensin system (RAS) depend on the availability of angiotensinogen (AGT) which generates angiotensin I (Ang I) when cleaved by renin. Thus, quantification of the intact AGT (iAGT) concentrations is important to evaluate the actual renin substrate available. The iAGT conformation exists as oxidized AGT (oxi-AGT) and reduced AGT (red-AGT) in a disulfide bond, and oxi-AGT has a higher affinity for renin, which may exacerbate RAS associated diseases. Accordingly, we determined iAGT, oxi-AGT and red-AGT levels in plasma from rats and mice. Blood samples were obtained by...
Source: Am J Physiol Renal P... - August 10, 2016 Category: Urology & Nephrology Authors: Satou R, Kobori H, Katsurada A, Miyata K, Navar LG Tags: Am J Physiol Renal Physiol Source Type: research

An additive effect of anti-PAI-1 antibody to ACE inhibitor on slowing the progression of diabetic kidney disease.
Abstract While angiotensin II blockade slows the progression of diabetic nephropathy, current data suggest that it alone cannot stop disease process. New therapies or drug combinations will be required to further slow or halt disease progression. Inhibition of PAI-1 aimed at enhancing ECM degradation has been shown therapeutic potential in diabetic nephropathy. Here using a mouse model of type II diabetes, the maximally therapeutic dose of the PAI-1 neutralizing mouse monoclonal antibody (MEDI-579) was determined and compared with the maximally effective dose of enalapril. We then examined whether addition of the ...
Source: Am J Physiol Renal P... - August 10, 2016 Category: Urology & Nephrology Authors: Gu C, Zhang J, Noble NA, Peng XR, Huang Y Tags: Am J Physiol Renal Physiol Source Type: research

Phosphatase inhibition increases AQP2 accumulation in the rat IMCD apical plasma membrane.
In conclusion, PP1/PP2A regulates the phosphorylation and apical plasma membrane accumulation of AQP2 differently than PP2B. Serine-264 of AQP2 is a phosphorylation site that is regulated by both PP1/PP2A and PP2B. This dual regulatory pathway may suggest a previously unappreciated role for multiple phosphatases in the regulation of urine concentration. PMID: 27488997 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 3, 2016 Category: Urology & Nephrology Authors: Ren H, Yang B, Ruiz JA, Efe O, Ilori TO, Sands JM, Klein JD Tags: Am J Physiol Renal Physiol Source Type: research

Acute kidney injury induces hallmarks of polycystic kidney disease.
Abstract Acute kidney injury (AKI) and autosomal dominant polycystic kidney disease (ADPKD) are considered separate entities that both frequently cause renal failure. Since ADPKD appears to depend on Pc1- or Pc2-dosage mechanism, we investigated whether slow progression of cystogenesis in two Pkd1 transgenic mouse models can be accelerated with moderate ischemia-reperfusion injury (IRI). Transient unilateral left ischemic kidney in both non-transgenic and transgenic mice reproducibly develop tubular dilatations, cysts and typical PKD cellular defects within 3 months post-IRI. Similar onset and severity of IRI indu...
Source: Am J Physiol Renal P... - August 3, 2016 Category: Urology & Nephrology Authors: Kurbegovic A, Trudel M Tags: Am J Physiol Renal Physiol Source Type: research