Brown adipose tissue transplantation ameliorates diabetic nephropathy through the miR-30b pathway by targeting Runx1

Posted: 2021-10-19 19:00:00
Objective: Adipose tissue is a major source of circulating microRNAs (miRNAs) that can regulate target genes in distant organs. However, the role of brown adipose tissue (BAT) in diabetic kidney disease (DKD) is still unknown. We studied the original BAT miR-30b targeting two key fibrotic regulators, Runt-related transcription factor 1 (Runx1) and snail family zinc finger 1 (Snail1), to combat DKD. Methods: First, we transplanted healthy BAT from normal mouse donors into diabetic mice (induced by a high-fat diet and streptozotocin injection). In vitro, we observed extracellular vesicles (EVs) secreted from brown adipocytes. AgomiR-30b was directly administered to the BAT of diabetic mice twice weekly for 4 consecutive weeks. Next, the role of Runx1 in DKD was determined by using siRUNX1 or pCMV-RUNX1 in HK-2 cells and in diabetic mice treated with AAV9-U6-shRunx1 or AAV9-EF1a-Runx1. Results: BAT transplantation reactivated endogenous BAT activity in diabetic mice, increased circulating miR-30b levels and significantly ameliorated DKD. In TGFβ1-treated HK-2 cells, miR-30b expression was significantly suppressed. miR-30b overexpression markedly decreased fibronectin and downregulated Runx1 and Snail1 expression, while silencing of miR-30b had the opposite effects. Next, Runx1 knockdown and overexpression mimicked the above phenotype of miR-30b mimics and inhibitors, respectively, both in vitro and in vivo. Moreover, Runx1 promoted TGFβ1-induced fibrosis by upregulating the PI3K pathway. Conclusion: BAT-derived miRNAs might be a promising target for kidney protection in diabetes mellitus. Keywords: Brown adipose tissue; Diabetic nephropathy; Runx1; Transplantation; miR-30b.

参考サイト PubMed: exsome

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9月 18, 2019 バイオアソシエイツ


健康な心筋組織を保護することで損傷を減らす心臓発作の直後に服用できる薬があると想像して欲しい。 心臓発作が起きた場合、心臓の専門医は、「時は筋肉なり」と言うと、バージニア工科大学カリリオン心臓医療センター・フラリン生物医学研究所のディレクターであるRobert Gourdie博士(写真)は語った。 血流によって酸素が供給されないと、心臓細胞はすぐに死ぬ。…

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