Abstract | 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:
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Authors | Yudan Zhang, Yingying Cai, Hongbin Zhang, Jiajun Zhang, Yanmei Zeng, Cunxia Fan, Shaozhou Zou, Chunyan Wu, Shu Fang, Ping Li, Xiaochun Lin, Ling Wang, Meiping Guan |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 125
Pg. 154916
(12 2021)
ISSN: 1532-8600 [Electronic] United States |
PMID | 34666067
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Core Binding Factor Alpha 2 Subunit
- MIRN30b microRNA, mouse
- MicroRNAs
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Topics |
- Adipose Tissue, Brown
(transplantation)
- Animals
- Core Binding Factor Alpha 2 Subunit
(metabolism)
- Diabetes Mellitus, Experimental
(metabolism)
- Diabetic Nephropathies
(metabolism, therapy)
- Diet, High-Fat
- Kidney
(metabolism)
- Male
- Mice
- MicroRNAs
(metabolism)
- Signal Transduction
(physiology)
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