ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
P2Y12 inhibitor clopidogrel inhibits renal fibrosis by blocking macrophage-to-myofibroblast transition.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 85 citations in OpenAlex.
- STK40 inhibits profibrotic Arg1Acta pharmacologica Sinica · 2026Article
- Macrophage-to-myofibroblast transition-derived itaconate promotes bone metastasis in lung cancer through targeting of HSPA8.Experimental & molecular medicine · 2026Article
- Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Attenuate Renal Fibrosis by Suppressing Fibroblast Activation via the INHBA/PI3K/AKT Pathway.Pediatric discovery · 2026Article
- Gastric cancer-secreted galectin-1 promotes peritoneal mesothelial-mesenchymal transition to prime peritoneal metastasis soil.iScience · 2026Article
- Identification of an immediate-early gene-activated fibroblast state in frozen shoulder capsular fibrosis.iScience · 2026Article
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- Curcumin Inhibits Renal Fibrosis by Suppressing S100A8/A9-TLR4 Signaling via Gut Microbiota-Derived Short-Chain Fatty Acid in Macrophages.Molecular nutrition & food research · 2026Article
- ASCL2-mediated macrophage-myofibroblast transition generates immunosuppressive CAF_7 in NSCLC bone metastases.Journal of experimental & clinical cancer research : CR · 2026Article
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- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Macrophage RNA polymerase II subunit 5-mediating protein deficiency exacerbates kidney inflammation and fibrosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
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- The role of the vascular niche in regulating kidney tubulointerstitial fibrosis.Kidney international · 2026Review
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- Targeting Macrophage-Mediated Mechanisms in Sepsis-Induced Cardiomyopathy: From Pathophysiology to Therapeutic Strategies.Journal of inflammation research · 2026Review
- Dapagliflozin attenuates diabetic renal fibrosis by inhibiting macrophage-myofibroblast transitionPeerJ · 2026Article
- BMAL1 regulates tubular epithelial-derived exosomal miR-27a-3p to inhibit macrophage-myofibroblast transition and alleviate ischemia/reperfusion-induced renal fibrosis.Theranostics · 2026Article
- Bone Marrow-Derived Macrophage NLRP3 Mediates Renal Fibrosis by triggering TGF-β/Smad3-mediated Macrophage-Myofibroblast Transition.International journal of biological sciences · 2026Article
- Targeting Macrophage-to-Myofibroblast Transition Mitigates Progression from Inflammation to Fibrosis in Rosacea.International journal of biological sciences · 2026Article
- Association between clopidogrel use and improved survival in critically ill patients with acute kidney injury: insights from MIMIC-IV database.BMC nephrology · 2025Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clopidogrel, a P2Y12 inhibitor, is a novel anti-fibrosis agent for chronic kidney disease (CKD), but its mechanisms remain unclear, which we investigated by silencing P2Y12 or treating unilateral ureteral obstruction (UUO) in LysM-Cre/Rosa Tomato mice with clopidogrel in vivo and in vitro. We found that P2Y12 was significantly increased and correlated with progressive renal fibrosis in CKD patients and UUO mice. Phenotypically, up to 82% of P2Y12-expressing cells within the fibrosing kidney were of macrophage origin, identified by co-expressing CD68/F4/80 antigens or a macrophage-lineage-tracing marker Tomato. Unexpectedly, more than 90% of P2Y12-expressing macrophages were undergoing macrophage-to-myofibroblast transition (MMT) by co-expressing alpha smooth muscle actin (α-SMA), which was also confirmed by single-cell RNA sequencing. Functionally, clopidogrel improved the decline rate of the estimated glomerular filtration rate (eGFR) in patients with CKD and significantly inhibited renal fibrosis in UUO mice. Mechanistically, P2Y12 expression was induced by transforming growth factor β1 (TGF-β1) and promoted MMT via the Smad3-dependent mechanism. Thus, silencing or pharmacological inhibition of P2Y12 was capable of inhibiting TGF-β/Smad3-mediated MMT and progressive renal fibrosis in vivo and in vitro. In conclusion, P2Y12 is highly expressed by macrophages in fibrosing kidneys and mediates renal fibrosis by promoting MMT via TGF-β/Smad3 signaling. Thus, P2Y12 inhibitor maybe a novel and effective anti-fibrosis agent for CKD.
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