ArticleAmerican journal of physiology. Renal physiology2015
Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via uPAR-mediated β1-integrin endocytosis.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- The Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) as Predictive Tool in Hospitalised Patients With Community-Acquired Pneumonia (CAP).The clinical respiratory journal · 2025Trial
- Alternative Splicing in Mechanically Stretched Podocytes as a Model of Glomerular Hypertension.Journal of the American Society of Nephrology : JASN · 2025Article
- Aberrant localization of β1 integrin in podocyte cytoplasm of primary FSGS with cellular lesion.Virchows Archiv : an international journal of pathology · 2025Article
- Podocyte senescence: from molecular mechanisms to therapeutics.Renal failure · 2024Review
- Role of plasminogen activated inhibitor-1 in the pathogenesis of anticoagulant related nephropathy.Frontiers in nephrology · 2024Article
- Clinicopathological differences in focal segmental glomerulosclerosis depending on the accompanying pathophysiological conditions in renal allografts.Virchows Archiv : an international journal of pathology · 2023Article
- Article
- Focal Segmental Sclerosis Associated with the Novel Multi-tyrosine Kinase Inhibitor Ponatinib.Internal medicine (Tokyo, Japan) · 2023Article
- Dual inhibition of the endothelin and angiotensin receptor ameliorates renal and inner ear pathologies in Alport mice.The Journal of pathology · 2023Article
- Alternatively Spliced Landscape of PPARγ mRNA in Podocytes Is Distinct from Adipose Tissue.Cells · 2022Article
- The Perspective of Vitamin D on suPAR-Related AKI in COVID-19.International journal of molecular sciences · 2022Review
- Diverse Alterations of Glomerular Capillary Networks in Focal Segmental Glomerular Sclerosis.Kidney international reports · 2022Article
- Pregnancy-onset thrombotic thrombocytopenic purpura with nephrotic syndrome: a case report.CEN case reports · 2022Article
- Podocyte Endocytosis in Regulating the Glomerular Filtration Barrier.Frontiers in medicine · 2022Review
- Soluble urokinase plasminogen activator receptor is associated with short-term mortality and enhanced reactive oxygen species production in acute-on-chronic liver failure.BMC gastroenterology · 2021Article
- Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1.EMBO molecular medicine · 2021Article
- Prognostic value of suPAR and hsCRP on acute kidney injury after cardiac surgery.BMC nephrology · 2021Observational
- WNT-β-catenin signalling - a versatile player in kidney injury and repair.Nature reviews. Nephrology · 2021Review
- Nephrotic syndrome with focal segmental glomerular lesions unclassified by Columbia classification; Pathology and clinical implication.PloS one · 2021Article
- Mechanisms of Scarring in Focal Segmental Glomerulosclerosis.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Review
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Podocyte-endothelial cell cross-talk is paramount for maintaining the filtration barrier. The present study investigated the endothelial response to podocyte injury and its subsequent role in glomerulosclerosis using the podocyte-specific injury model of NEP25/LMB2 mice. NEP25/LMB2 mice showed proteinuria and local podocyte loss accompanied by thrombotic microangiopathy on day 8. Mice showed an increase of glomerular plasminogen activator inhibitor type 1 (PAI-1) mRNA and aberrant endothelial PAI-1 protein already on day 1, before thrombosis and proteinuria. A PAI-1-specific inhibitor reduced proteinuria and thrombosis and preserved podocyte numbers in NEP25/LMB2 mice by stabilization of β1-integrin translocation. Heparin loading significantly reduced thrombotic formation, whereas proteinuria and podocyte numbers were unchanged. Immortalized podocytes treated with PAI-1 and the urokinase plasminogen activator (uPA) complex caused significant cell detachment, whereas podocytes treated with PAI-1 or uPA alone or with the PAI-1/uPA complex pretreated with an anti-uPA receptor (uPAR) antibody failed to cause detachment. Confocal microscopy and cell surface biotinylation experiments showed that internalized β1-integrin was found together with uPAR in endocytotic vesicles. The administration of PAI-1 inhibitor or uPAR-blocking antibody protected cultured podocytes from cell detachment. In conclusion, PAI-1/uPA complex-mediated uPAR-dependent podocyte β1-integrin endocytosis represents a novel mechanism of glomerular injury leading to progressive podocytopenia. This aberrant cross-talk between podocytes and endothelial cells represents a feedforward injury response driving podocyte loss and progressive glomerulosclerosis.
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