The Proximal Tubule is the Primary Target of Injury and Progression of Kidney Disease: Role of the glomerulotubular junction.

The Proximal Tubule is the Primary Target of Injury and Progression of Kidney Disease: Role of the glomerulotubular junction. Am J Physiol Renal Physiol. 2016 May 18;:ajprenal.00164.2016 Authors: Chevalier RL Abstract There is an alarming global increase in the incidence of end-stage kidney disease, for which early biomarkers and effective treatment options are lacking. Largely based on the histology of the end-stage kidney and on the model of unilateral ureteral obstruction, current investigation is focused on the pathogenesis of renal interstitial fibrosis as a central mechanism in the progression of chronic kidney disease (CKD). It is now recognized that cumulative episodes of acute kidney injury (AKI) can lead to CKD and conversely, CKD is a risk factor for AKI. Based on recent and historic studies, this review shifts attention from the glomerulus and interstitium to the proximal tubule as the primary sensor and effector in the progression of CKD as well as AKI. Packed with mitochondria and dependent on oxidative phosphorylation, the proximal tubule is particularly vulnerable to injury (obstructive, ischemic, hypoxic, oxidative, metabolic), resulting in cell death and ultimately in the formation of atubular glomeruli. Animal models of human glomerular and tubular disorders have provided evidence for a broad repertoire of morphologic and functional responses of the proximal tubule, revealing processes of degeneration and repair that may lead to new th...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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In conclusion, PT ATR activation is a key component of the DDR, which confers a protective effect mitigating the maladaptive repair and consequent fibrosis that follow kidney injury.
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
AbstractObstructive nephropathy is a common cause for chronic kidney disease. Surgery, which is adopted to promptly relieve the obstruction, is the most important method to save damaged kidneys. However, earlier studies have shown that renal function will continue to deteriorate until the terminal stage after the obstruction ’ relief. The aim of this study is to explore the renal fibrosis and investigate the effect of losartan on renal fibrosis after the obstruction’ relief using an improved mouse model of relief for unilateral ureteral obstruction (RUUO). Experiments carried out using C57BL/6 mice (n =&...
Source: International Urology and Nephrology - Category: Urology & Nephrology Source Type: research
Therapeutic Targeting of Fibrotic Epithelial-Mesenchymal Transition–An Outstanding Challenge Attila Fintha1, Ákos Gasparics2, László Rosivall3 and Attila Sebe3,4* 12nd Department of Pathology, Semmelweis University, Budapest, Hungary 21st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary 3Department of Pathophysiology, International Nephrology Research and Training Center, Semmelweis University, Budapest, Hungary 4Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany Back in 1995, a landmark paper was published, which shaped the fi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In conclusion, our data indicate the potent therapeutic of BPS in mitigating fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT) progression after inhibiting inflammatory and oxidative stress effects.Key messagesBPS could improve renal recovery through anti-inflammatory and anti-oxidative pathways.BPS could mitigate fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT).
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research
In conclusion, our data indicate the potent therapeutic of BPS in mitigating fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT) progression after inhibiting inflammatory and oxidative stress effects. KEY MESSAGES: BPS could improve renal recovery through anti-inflammatory and anti-oxidative pathways. BPS could mitigate fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT). PMID: 30923844 [PubMed - as supplied by publisher]
Source: Molecular Medicine - Category: Molecular Biology Authors: Tags: J Mol Med (Berl) Source Type: research
Congenital obstructive nephropathy is a major cause of chronic kidney disease in children. The contribution of changes in the identity of renal cells to the pathology of obstructive nephropathy is poorly understood. Using a partial unilateral ureteral obstruction model in genetically modified neonatal mice, we traced the fate of cells derived from the renal stroma, cap mesenchyme, ureteric bud epithelium and podocytes using Foxd1Cre , Six2Cre , HoxB7Cre and Podocyte.Cre mice respectively, crossed with double fluorescent reporter (mT/mG) mice. Persistent obstruction leads to a significant loss of tubular epithelium, rarefac...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research
Plasminogen activator inhibitor-1 (PAI-1) expression is highly upregulated in tubular and interstitial cells during obstructive uropathy (i.e., nephrolithiasis, ureteral stricture) and is linked to kidney fibrosis. Precise mechanisms whereby PAI-1 contributes to renal injury, however, are unknown and, surprisingly, appear to be urokinase-type plasminogen activator independent. Here, we test the hypothesis that sustained PAI-1 expression in renal epithelial cells promotes renal tubular dysfunction and maladaptive repair critical for chronic kidney disease progression.
Source: The Journal of Urology - Category: Urology & Nephrology Authors: Tags: Infections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I Source Type: research
Conclusion: These data suggest that gender may influence the worsening of pulmonary mechanics and renal function in UUO animals and the LLLT can improve the lung elastances, renal function and fibrosis.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Mechanisms of Lung Injury and Repair Source Type: research
Publication date: Available online 20 January 2017 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Author(s): Una Bhreathnach, Brenda Griffin, Eoin Brennan, Leah Ewart, Debra Higgins, Madeline Murphy The highly conserved mitochondrial protein induced in high glucose-1 (IHG-1) functions to maintain mitochondrial quality and is associated with the development of fibrosis in diabetic nephropathy. Towards identifying novel approaches to treating diabetic kidney disease, IHG-1-protein-protein interactions were investigated using epitope-tagged immunoprecipitation analyses followed by mass spectrometry. ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Abstract The highly conserved mitochondrial protein induced in high glucose-1 (IHG-1) functions to maintain mitochondrial quality and is associated with the development of fibrosis in diabetic nephropathy. Towards identifying novel approaches to treating diabetic kidney disease, IHG-1-protein-protein interactions were investigated using epitope-tagged immunoprecipitation analyses followed by mass spectrometry. Here we show that IHG-1 is solely expressed in mitochondria and localised to the inner mitochondrial membrane, the region where mitochondrial reactive oxygen species are generated. Chaperones HSPA5 and TRAP1...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Tags: Biochim Biophys Acta Source Type: research
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