ArticleThe American journal of pathology2010
tPA is a potent mitogen for renal interstitial fibroblasts: role of beta1 integrin/focal adhesion kinase signaling.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Roles of tissue plasminogen activator in chronic subdural hematoma, independent of the fibrinolytic system.Neurosurgical review · 2026Article
- Matrix metalloproteinases in kidney homeostasis and diseases: an update.American journal of physiology. Renal physiology · 2024Review
- Cell Cycle Dysregulation and Renal Fibrosis.Frontiers in cell and developmental biology · 2021Review
- Total Glucosides of Paeony Alleviate Cell Apoptosis and Inflammation by Targeting the Long Noncoding RNA XIST/MicroRNA-124-3p/ITGB1 Axis in Renal Ischemia/Reperfusion Injury.Mediators of inflammation · 2020Article
- A conditionally immortalized Gli1-positive kidney mesenchymal cell line models myofibroblast transition.American journal of physiology. Renal physiology · 2019Article
- Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2017Article
- GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-β-Induced Smad3 Phosphorylation.Journal of the American Society of Nephrology : JASN · 2015Article
- Components of the plasminogen activation system promote engraftment of porous polyethylene biomaterial via common and distinct effects.PloS one · 2015Article
- Sonic hedgehog is a novel tubule-derived growth factor for interstitial fibroblasts after kidney injury.Journal of the American Society of Nephrology : JASN · 2014Article
- Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy.Kidney international · 2014Article
- Rheb/mTORC1 signaling promotes kidney fibroblast activation and fibrosis.Journal of the American Society of Nephrology : JASN · 2013Article
- Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis.Frontiers in endocrinology · 2013Article
- Matrix metalloproteinases in kidney homeostasis and diseases.American journal of physiology. Renal physiology · 2012Review
- Response gene to complement 32 is essential for fibroblast activation in renal fibrosis.The Journal of biological chemistry · 2011Article
- Cellular and molecular mechanisms of renal fibrosis.Nature reviews. Nephrology · 2011Review
- Targeted inhibition of β-catenin/CBP signaling ameliorates renal interstitial fibrosis.Journal of the American Society of Nephrology : JASN · 2011Article
- Inhibition of proinflammatory RANTES expression by TGF-beta1 is mediated by glycogen synthase kinase-3beta-dependent beta-catenin signaling.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Proliferation and expansion of interstitial fibroblasts are predominant features of progressive chronic kidney diseases. However, how interstitial fibroblast proliferation is controlled remains ambiguous. Here we show that tissue-type plasminogen activator (tPA) is a potent mitogen that promotes interstitial fibroblast proliferation through a cascade of signaling events. In vitro, tPA promoted cell proliferation of rat kidney fibroblasts (NRK-49F), as assessed by cell counting, cell proliferation assay, and bromodeoxyuridine labeling. tPA also accelerated NRK-49F cell cycle progression. Fibroblast proliferation induced by tPA was associated with an increased expression of numerous proliferation-related genes, including c-fos, c-myc, proliferating cell nuclear antigen, and cyclin D1. The mitogenic effect of tPA was independent of its protease activity, but required LDL receptor-related protein 1. Interestingly, inhibition of beta1 integrin signaling prevented tPA-mediated fibroblast proliferation. tPA rapidly induced tyrosine phosphorylation of focal adhesion kinase (FAK), which led to activation of its downstream mitogen-activated protein kinase signaling. Blockade of FAK, but not integrin-linked kinase, abolished the tPA-triggered extracellular signal-regulated protein kinase 1/2 activation, proliferation-related gene induction, and fibroblast proliferation. In vivo, proliferation of interstitial myofibroblasts in tPA null mice was attenuated after obstructive injury, compared with the wild-type controls. These studies illustrate that tPA is a potent mitogen that promotes renal interstitial fibroblast proliferation through LDL receptor-related protein 1-mediated beta1 integrin and FAK signaling.
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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.