ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2019
Fibroblast-specific plasminogen activator inhibitor-1 depletion ameliorates renal interstitial fibrosis after unilateral ureteral obstruction.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Multi-omics profiling reveals EMT-driven fibroblast activation in the renal injury niche.Cellular and molecular life sciences : CMLS · 2026Article
- Tissue-resident macrophage survival depends on mitochondrial function regulated by SerpinB2 in chronic inflammation.Nature communications · 2026Article
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis.International journal of molecular sciences · 2023Review
- Poricoic acid A suppresses renal fibroblast activation and interstitial fibrosis in UUO rats via upregulating Sirt3 and promoting β-catenin K49 deacetylation.Acta pharmacologica Sinica · 2023Article
- Intestinal Lymphatic Dysfunction in Kidney Disease.Circulation research · 2023Review
- Myofibroblast depletion reduces kidney cyst growth and fibrosis in autosomal dominant polycystic kidney disease.Kidney international · 2023Article
- The role of mineralocorticoid receptor activation in kidney inflammation and fibrosis.Kidney international supplements · 2022Review
- Identification of an unrecognized circRNA associated with development of renal fibrosis.Frontiers in genetics · 2022Article
- Kidney injury-mediated disruption of intestinal lymphatics involves dicarbonyl-modified lipoproteins.Kidney international · 2021Article
- PAI-1 induction during kidney injury promotes fibrotic epithelial dysfunction via deregulation of klotho, p53, and TGF-β1-receptor signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Verbascoside alleviates renal fibrosis in unilateral ureteral obstruction rats by inhibiting macrophage infiltration.Iranian journal of basic medical sciences · 2021Article
- WNT-β-catenin signalling - a versatile player in kidney injury and repair.Nature reviews. Nephrology · 2021Review
- Induction and transmission of oncogene-induced senescence.Cellular and molecular life sciences : CMLS · 2021Review
- Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis.Frontiers in pharmacology · 2021Review
- Neural transcription factor Pou4f1 promotes renal fibrosis via macrophage-myofibroblast transition.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Targeting the progression of chronic kidney disease.Nature reviews. Nephrology · 2020Review
- Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.Frontiers in pharmacology · 2019Review
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10 authors.
Funding
Abstract
backgroundPlasminogen activator inhibitor-1 (PAI-1) expression increases extracellular matrix deposition and contributes to interstitial fibrosis in the kidney after injury. While PAI-1 is ubiquitously expressed in the kidney, we hypothesized that interstitial fibrosis is strongly dependent on fibroblast-specific PAI-1 (fbPAI-1).
methodsTenascin C Cre (TNC Cre) and fbPAI-1 knockdown (KD) mice with green fluorescent protein (GFP) expressed within the TNC construct underwent unilateral ureteral obstruction and were sacrificed 10 days later.
resultsGFP+ cells in fbPAI-1 KD mice showed significantly reduced PAI-1 expression. Interstitial fibrosis, measured by Sirius red staining and collagen I western blot, was significantly decreased in fbPAI-1 KD compared with TNC Cre mice. There was no significant difference in transforming growth factor β (TGF-β) expression or its activation between the two groups. However, GFP+ cells from fbPAI-1 KD mice had lower TGF β and connective tissue growth factor (CTGF) expression. The number of fibroblasts was decreased in fbPAI-1 KD compared with TNC Cre mice, correlating with decreased alpha smooth muscle actin (α-SMA) expression and less fibroblast cell proliferation. TNC Cre mice had decreased E-cadherin, a marker of differentiated tubular epithelium, in contrast to preserved expression in fbPAI-1 KD. F4/80-expressing cells, mostly CD11c+/F4/80+ cells, were increased while M1 macrophage markers were decreased in fbPAI-1 KD compared with TNC Cre mice.
conclusionThese findings indicate that fbPAI-1 depletion ameliorates interstitial fibrosis by decreasing fibroblast proliferation in the renal interstitium, with resulting decreased collagen I. This is linked to decreased M1 macrophages and preserved tubular epithelium.
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