期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 529, 期 1, 页码 119-125出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.05.148
关键词
Vascular smooth muscle; microRNA; Insulin; Glucose; miR-145; IRS-1
资金
- Novo Nordisk Foundation
- Swedish Research Council
- Crafoord Foundation
- Swedish Heart and Lung Foundation
- Royal Physiographic Society
- Magnus Bergvall foundation
Regulation of insulin signaling by microRNAs in smooth muscle cells may contribute to diabetic vascular disease. The two smooth muscle enriched miRNAs miR-143 and miR-145 have been reported to target mediators of insulin signaling in non-smooth muscle cells. In this study, we aimed to determine the importance of this regulation in vascular smooth muscle cells, where expression of miR-143/145 is much higher than in other cell types. Smooth muscle cells deficient of the miR-143/145 cluster were used, as well as smooth muscle cells transfected with mimics/inhibitors for either miR-143 or miR-145. We found that deletion of miR-143/145 in smooth muscle results in a dramatic upregulation IRS-1 expression and insulin signaling, and an increased insulin-induced glucose uptake. Furthermore, specific modulation of either miR-145 or miR-143 expression regulated specific targets (IRS-1, ORP8 and the IGF-1 receptor) in the insulin signaling pathway. Consequently, transient inhibition or overexpression of either miR-143 or miR-145 was sufficient to regulate insulin signaling in smooth muscle cells. In conclusion, the results of this study support an important role for both miR-143 and miR-145 in the regulation of insulin signaling and glucose uptake in vascular smooth muscle cells. (C) 2020 The Authors. Published by Elsevier Inc.
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