ArticleStem cell research & therapy2020
Extracellular vesicles produced by bone marrow mesenchymal stem cells attenuate renal fibrosis, in part by inhibiting the RhoA/ROCK pathway, in a UUO rat model.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- The Nephroprotective Properties of Extracellular Vesicles in Experimental Models of Chronic Kidney Disease: a Systematic Review.Stem cell reviews and reports · 2022Pooled it
- The dual role of exosomes in renal fibrosis and their potential for clinical translational applications.Renal failure · 2026Review
- Leveraging extracellular vesicle biology for novel tests and therapeutics for kidney fibrosis.Clinical and translational medicine · 2026Review
- [Current status of intrauterine adhesion treatment and research progress in stem cell therapy].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Substrate Stiffness Modulates Fibroblast Extracellular Vesicle Secretion Via Mechanotransduction Pathways.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Neuroprotective effects of Berberine-loaded BMSCs-apoptotic extracellular vesicles on retinal ganglion cells: therapeutic potential for glaucomatous injury.Journal of nanobiotechnology · 2025Article
- Lactate and Lactylation in AKI-to-CKD: Epigenetic Regulation and Therapeutic Opportunities.Cell proliferation · 2025Review
- Advances and challenges in kidney fibrosis therapeutics.Nature reviews. Nephrology · 2025Review
- Phosphatidylserine-mediated uptake of extracellular vesicles by hepatocytes ameliorates liver ischemia-reperfusion injury.Apoptosis : an international journal on programmed cell death · 2025Article
- Extracellular Vesicles in Acute Kidney Injury: Mechanisms, Biomarkers, and Therapeutic Potential.International journal of nanomedicine · 2025Review
- Mesenchymal stem cells derived extracellular vesicles for chronic kidney disease: pleiotropic mechanisms of actions of a versatile therapy.Frontiers in bioengineering and biotechnology · 2025Review
- Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis-Associated Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Stem cell-based therapy for fibrotic diseases: mechanisms and pathways.Stem cell research & therapy · 2024Review
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- Comparative study of systemic and local delivery of mesenchymal stromal cells for the treatment of chronic kidney disease.Frontiers in cell and developmental biology · 2024Article
- Engineered inhaled nanocatalytic therapy for ischemic cerebrovascular disease by inducing autophagy of abnormal mitochondria.NPJ Regenerative medicine · 2023Article
- Naïve or Engineered Extracellular Vesicles from Different Cell Sources: Therapeutic Tools for Kidney Diseases.Pharmaceutics · 2023Review
- Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases.Journal of nanobiotechnology · 2023Review
- Analysis of the potential biological mechanisms of diosmin against renal fibrosis based on network pharmacology and molecular docking approach.BMC complementary medicine and therapies · 2023Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExtracellular vesicles produced by bone marrow mesenchymal stem cells (BMSC-EVs) can play important roles in the repair of injured tissues. Though numerous studies have reported the effect of EVs on renal fibrosis, the underlying mechanisms remain unclear. We hypothesized that BMSC-EVs containing milk fat globule-epidermal growth factor-factor 8 (MFG-E8) could attenuate renal fibrosis by inhibiting the RhoA/ROCK pathway.
methodsWe investigated whether BMSC-EVs have anti-fibrotic effects in a rat model of renal fibrosis, in which rats were subjected to unilateral ureteral obstruction (UUO), as well as in cultured HK2 cells. Extracellular vesicles from BMSCs were collected and co-cultured with HK2 cells during transforming growth factor-β1 (TGF-β1) treatment. HK2 cells co-cultured with TGF-β1 were also treated with the ROCK inhibitor, Y-27632.
resultsCompared with the Sham group, UUO rats displayed fibrotic abnormalities, accompanied by an increased expression of α-smooth muscle actin and Fibronectin and reduced expression of E-cadherin. These molecular and pathological changes suggested increased inflammation in damaged kidneys. Oxidative stress, as evidenced by an increased level of MDA and decreased levels of SOD1 and Catalase, was also observed in UUO kidneys. Additionally, activation of cleaved caspase-3 and PARP1 and increased apoptosis in the proximal tubules confirmed tubular cell apoptosis in the UUO group. All of these phenotypes exhibited by UUO rats were suppressed by treatment with BMSC-EVs. However, the protective effect of BMSC-EVs was completely abolished by the inhibition of MFG-E8. Consistent with the in vivo results, treatment with BMSC-EVs reduced inflammation, oxidative stress, apoptosis, and fibrosis in HK-2 cells stimulated with TGF-β1 in vitro. Interestingly, treatment with Y-27632 protected HK-2 cells against inflammation and fibrosis, although oxidative stress and apoptosis were unchanged.
conclusionsOur results show that BMSC-EVs containing MFG-E8 attenuate renal fibrosis in a rat model of renal fibrosis, partly through RhoA/ROCK pathway inhibition.
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