ArticleCell death & disease2020
Drp1-mediated mitochondrial fission promotes renal fibroblast activation and fibrogenesis.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 128 citations in OpenAlex.
- RhoA through its various effectors mediate mitochondrial fragmentation in polycystic kidney disease.iScience · 2026Article
- Mitochondrial dysfunction of renal tubular epithelial cells in chronic kidney disease-associated fibrosis: from organelle homeostasis to multicellular remodeling.Molecular biology reports · 2026Review
- Aerobic Exercise Ameliorates Renal Injury in High-Fat Diet-Fed Mice: A Novel Effect Mediated by the Drp1-mtROS Pathway.Acta physiologica (Oxford, England) · 2026Article
- Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder.Nature reviews. Nephrology · 2026Review
- Mitochondrial heterogeneity across cardiac cell types in heart failure with preserved ejection fraction.Redox biology · 2026Review
- ZhuJing Pill retards lens-induced myopia progression by improving ciliary muscle mitochondrial function via KEAP1/NRF2-TGF-β axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Trimethylamine N-oxide activates cardiac fibroblasts transformation through NLRP3 inflammasome activation with changes in mitochondrial dynamics and ER-mitochondrial contact under ER stress.Molecular and cellular biochemistry · 2026Article
- Bazi Bushen Capsule restores fertility by targeting mitochondrial health in aging endometrium.iMeta · 2026Article
- Qingda Granule and Its Individual Herbs Inhibit Hypertension-Induced Vascular Smooth Muscle Cells Proliferation via ERK and JNK Pathways.Chinese journal of integrative medicine · 2026Article
- S100A9 Aggravates Cardiac Fibrosis by TLR4/PGC-1α Mediated Macrophage-Myofibroblast Crosstalk.Journal of extracellular vesicles · 2026Article
- Targeting YAP: mechanistic breakthroughs and therapeutic prospects in reversing organ fibrosis.Molecular and cellular biochemistry · 2026Review
- Review
- Article
- Omega-3 Fatty Acids Attenuate Renal Myostatin Expression and Mitochondrial Alterations Under Uremic Conditions.International journal of molecular sciences · 2026Article
- Kisspeptin exacerbates androgen-induced follicular dysplasia by promoting Drp1 phosphorylation imbalance and mitochondrial excessive fission in granulosa cells of polycystic ovary syndrome.Journal of ovarian research · 2026Article
- Direct coupling and protective activation of DRP1 by the DNA-PKcs inhibitor KU-57788 synergizes with ferroptosis in anaplastic thyroid cancer cells.Cell death & disease · 2026Article
- IFFO1 inhibits breast cancer by coordinating mitochondrial fission and fatty acid synthesis via the LaminA/C-PGC1α axis.Oncogenesis · 2026Article
- NNMT Orchestrates Metabolic-Epigenetic Reprogramming to Drive Macrophage-Myofibroblast Transition in Hypertrophic Scarring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitophagy and oxidative stress in chronic kidney disease (Review).Molecular medicine reports · 2026Review
- SETDB2 Mitigates Podocyte Dysfunction in Diabetic Kidney Disease Through Epigenetic Silencing of SMAD3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive mitochondrial fission acts as a pro-proliferative marker in some cancers and organ fibrosis; its potential role in renal fibroblast activation and fibrogenesis has never been investigated. Here, we showed more pronounced fragmented mitochondria in fibrotic than in non-fibrotic renal fibroblast in humans and mice. In a mouse model of obstructive nephropathy, phosphorylation of Drp1 at serine 616 (p-Drp1S616) and acetylation of H3K27(H3K27ac) was increased in fibrotic kidneys; pharmacological inhibition of mitochondrial fission by mdivi-1 substantially reduced H3K27ac levels, fibroblasts accumulation, and interstitial fibrosis. Moreover, mdivi-1 treatment was able to attenuate the established renal fibrosis. In cultured renal interstitial fibroblasts, targeting Drp1 using pharmacological inhibitor or siRNA suppressed TGF-β1-elicited cell activation and proliferation, as evidenced by inhibiting expression of α-smooth muscle actin (α-SMA) and collagen I, as well as by reducing DNA synthesis. In contrast, Drp1 deletion enhanced cell apoptosis, along with decreased mitochondrial fragmentation, mtROS elevation, and glycolytic shift upon TGF-β1 stimulation. In Drp1 deletion fibroblasts, re-expression of wild-type Drp1 rather than Drp1S616A mutant restores the reduction of TGF-β-induced-Drp1 phosphorylation, H3K27ac, and cell activation. Moreover, TGF-β1 treatment increased the enrichment of H3K27ac at the promoters of α-SMA and PCNA, which was reversed in Drp1-knockdown fibroblasts co-transfected with empty vector or Drp1S616A, but not wild-type Drp1. Collectively, our results imply that inhibiting p-Drp1S616-mediated mitochondrial fission attenuates fibroblast activation and proliferation in renal fibrosis through epigenetic regulation of fibrosis-related genes transcription and may serve as a therapeutic target for retarding progression of chronic kidney disease.
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