Adipose mesenchymal stem cell-derived extracellular vesicles containing microRNA-26a-5p target TLR4 and protect against diabetic nephropathy.
作者： Yurui Duan , Qingyang Luo , Yun Wang , Yali Ma , Fang Chen
关键词: Antagomir 、 Viability assay 、 Cancer research 、 Cell culture 、 Flow cytometry 、 Vascular endothelial growth factor A 、 Mesenchymal stem cell 、 Cellular differentiation 、 Adipose tissue 、 Biology
摘要: Diabetic nephropathy (DN) is a complication of diabetes that increasing in prevalence China. Extracellular vesicles (EVs) carrying microRNAs (miRs) may represent useful tool the development therapies for DN. Here, we report EVs released by adipose-derived mesenchymal stem cells (ADSCs) during DN contain microRNA, miR-26a-5p, suppresses Using bioinformatic analyses, identified differentially expressed miRs from ADSCs and predicted downstream regulatory target genes. We isolated (MSCs) adipose tissues collected ADSCs. exposed mouse glomerular podocytes MP5 to high glucose (HG), ADSC-derived EVs, miR-26a-5p inhibitor/antagomir, Toll-like receptor 4 (TLR4) plasmids, or NF-κB pathway activator (phorbol-12-myristate-13-acetate, PMA). used cell counting kit-8 (CCK-8) assay flow cytometry investigate impact on viability apoptosis validated results these assays with vivo experiments nude mice. found DN, at very low levels, whereas TLR4 highly expressed. Of note, ameliorated pathological symptoms diabetic mice transferred HG-induced cells, improving while suppressing cells. also protects injury targeting TLR4, inactivating pathway, downregulating vascular endothelial growth factor A (VEGFA). Moreover, podocytes, which pathology. These findings suggest against
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