ArticleKidney international2009
Biomechanical strain causes maladaptive gene regulation, contributing to Alport glomerular disease.
Article in Kidney international, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- Treatment Approaches for Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2026Review
- Mouse Alport podocytes are susceptible to AAV9 transduction in vivo.Kidney international · 2026Article
- Collagen IV in Gould syndrome and Alport syndrome.Nature reviews. Nephrology · 2025Review
- Pathological diagnosis of Alport syndrome.Kidney research and clinical practice · 2025Article
- Matrix metalloproteinases in kidney homeostasis and diseases: an update.American journal of physiology. Renal physiology · 2024Review
- Ramipril therapy in integrin α1-null, autosomal recessive Alport mice triples lifespan: mechanistic clues from RNA-seq analysis.The Journal of pathology · 2024Article
- Dual inhibition of the endothelin and angiotensin receptor ameliorates renal and inner ear pathologies in Alport mice.The Journal of pathology · 2023Article
- A novel nanoluciferase transgenic reporter measures proteinuria in zebrafish.Kidney international · 2022Article
- Glomerular basement membrane deposition of collagen α1(III) in Alport glomeruli by mesangial filopodia injures podocytes via aberrant signaling through DDR1 and integrin α2β1.The Journal of pathology · 2022Article
- Tensin 2-deficient nephropathy: mechanosensitive nephropathy, genetic susceptibility.Experimental animals · 2022Review
- Matrix Metalloproteinase-10 in Kidney Injury Repair and Disease.International journal of molecular sciences · 2022Review
- Molecular and Cellular Mechanisms Underlying the Initiation and Progression of Alport Glomerular Pathology.Frontiers in medicine · 2022Review
- Creation of X-linked Alport syndrome rat model with Col4a5 deficiency.Scientific reports · 2021Article
- Multidisciplinary Management of Alport Syndrome: Current Perspectives.Journal of multidisciplinary healthcare · 2021Review
- Pericyte abnormalities precede strial capillary basement membrane thickening in Alport mice.Hearing research · 2020Article
- Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- Basement Membrane Defects in Genetic Kidney Diseases.Frontiers in pediatrics · 2018Review
- Characterization of the early molecular changes in the glomeruli of Cd151Scientific reports · 2017Article
- The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Collagen IV diseases: A focus on the glomerular basement membrane in Alport syndrome.Matrix biology : journal of the International Society for Matrix Biology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with Alport's syndrome develop a number of pro-inflammatory cytokine and matrix metalloproteinase (MMP) abnormalities that contribute to progressive renal failure. Changes in the composition and structure of the glomerular basement membranes likely alter the biomechanics of cell adhesion and signaling in these patients. To test if enhanced strain on the capillary tuft due to these structural changes contributes to altered gene regulation, we subjected cultured podocytes to cyclic biomechanical strain. There was robust induction of interleukin (IL)-6, along with MMP-3, -9, -10, and -14, but not MMP-2 or -12 by increased strain. Neutralizing antibodies against IL-6 attenuated the strain-mediated induction of MMP-3 and -10. Alport mice treated with a general inhibitor of nitric oxide synthase (L-NAME) developed significant hypertension and increased IL-6 and MMP-3 and -10 in their glomeruli relative to those of normotensive Alport mice. These hypertensive Alport mice also had elevated proteinuria along with more advanced histological and ultrastructural glomerular basement membrane damage. We suggest that MMP and cytokine dysregulation may constitute a maladaptive response to biomechanical strain in the podocytes of Alport patients, thus contributing to glomerular disease initiation and progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.