ArticleThe Journal of clinical investigation2002
Disruption of tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive nephropathy.
Article in The Journal of clinical investigation, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 227 citations in OpenAlex.
- LYVE1 ectodomain shedding blunts lymphatic transmigration and clearance of macrophages during kidney injury.JCI insight · 2026Article
- Decursin ameliorates diabetic kidney disease by attenuating renal epithelial-mesenchymal transition via inhibition of the PI3K/Akt pathway.American journal of translational research · 2026Article
- Review
- Effects of caloric restriction and ketogenic diet on renal fibrosis after ischemia/reperfusion injury.Heliyon · 2023Article
- Macrophage Function Modulated by tPA Signaling in Mouse Experimental Kidney Disease Models.International journal of molecular sciences · 2023Review
- Bone marrow-derived mesenchymal stem cells transplantation ameliorates renal injury through anti-fibrotic and anti-inflammatory effects in chronic experimental renovascular disease.Biomedical journal · 2022Article
- The hepatocyte growth factor/c-met pathway is a key determinant of the fibrotic kidney local microenvironment.iScience · 2021Article
- Critical roles of SMYD2 lysine methyltransferase in mediating renal fibroblast activation and kidney fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Up-regulation of matrix metalloproteinases-9 in the kidneys of diabetic rats and the association with neutrophil gelatinase-associated lipocalin.BMC nephrology · 2021Article
- Review
- Increased fibrotic signaling in a murine model for intra-arterial contrast-induced acute kidney injury.American journal of physiology. Renal physiology · 2020Article
- Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.JCO precision oncology · 2020Article
- tPA promotes the proliferation of lung fibroblasts and activates the Wnt/β-catenin signaling pathway in idiopathic pulmonary fibrosis.Cell cycle (Georgetown, Tex.) · 2019Article
- Twist1 in Infiltrating Macrophages Attenuates Kidney FibrosisJournal of the American Society of Nephrology : JASN · 2019Article
- Selective inhibition of class IIa histone deacetylases alleviates renal fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Influence of hepatocyte growth factor-transfected bone marrow-derived mesenchymal stem cells towards renal fibrosis in rats.The Indian journal of medical research · 2019Article
- Traditional Chinese Medicine and regulatory roles on epithelial-mesenchymal transitions.Chinese medicine · 2019Review
- PAX2 may induce ADAM10 expression in renal tubular epithelial cells and contribute to epithelial-to-mesenchymal transition.International urology and nephrology · 2018Article
- FHL2 promotes tubular epithelial-to-mesenchymal transition through modulating β-catenin signalling.Journal of cellular and molecular medicine · 2018Article
- IL-17 Receptor Signaling Negatively Regulates the Development of Tubulointerstitial Fibrosis in the Kidney.Mediators of inflammation · 2018Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Tissue-type plasminogen activator (tPA) is one of the major components in the matrix proteolytic network whose role in the pathogenesis of renal interstitial fibrosis remains largely unknown. Here, we demonstrate that ablation of tPA attenuated renal interstitial fibrotic lesions in obstructive nephropathy. Mice lacking tPA developed less morphological injury and displayed a reduced deposition of interstitial collagen III and fibronectin as well as total tissue collagen in the kidneys after sustained ureteral obstruction, when compared with their wild-type counterparts. Deficiency of tPA selectively blocked tubular epithelial-to-myofibroblast transition (EMT), but did not affect myofibroblastic activation from interstitial fibroblasts. A marked decrease in matrix metalloproteinase-9 (MMP-9) induction was found in the obstructed kidneys of tPA(-/-) mice, which led to a dramatic preservation of the structural and functional integrity of tubular basement membrane (TBM). In vitro, tPA induced MMP-9 gene expression and protein secretion in renal interstitial fibroblasts. Thus, increased tPA is detrimental in renal interstitial fibrogenesis through a cascade of events that lead to MMP-9 induction, TBM destruction, and promotion of EMT. Our findings establish a crucial and definite importance of EMT in the pathogenesis of renal interstitial fibrosis at the whole-animal level.
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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.