Journal of Molecular Cell Biology

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miR-145 improves metabolic inflammatory disease through multiple pathways

Min He ^1,†, Nan Wu^1,2,† , Man Cheong Leong^1,†, Weiwei Zhang¹, Zi Ye¹, Rumei Li¹, Jinyang Huang¹, Zhaoyun Zhang¹, Lianxi Li¹, Xiao Yao¹, Wenbai Zhou¹, Naijia Liu¹, Zhihong Yang¹, Xuehong Dong¹, Yintao Li¹, Lili Chen¹, Qin Li¹, Xuanchun Wang¹, Jie Wen¹, Xiaolong Zhao¹, Bin Lu¹, Yehong Yang¹, Qinghua Wang ^1,3, and Renming Hu ^1,*

¹ Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Institute of Endocrinology and Diabetology, Fudan University, Shanghai, China
² Department of Geriatrics, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
³ Division of Endocrinology and Metabolism, the Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, Ontario, Canada
^† These authors contributed equally to this work.
^*Correspondence to:Renming Hu, E-mail: renminghu@fudan.edu.cn

J Mol Cell Biol, Volume 12, Issue 2, February 2020, 152-162, https://doi.org/10.1093/jmcb/mjz015

Keyword: type 2 diabetes, osteoprotegerin, Kruppel-like factor 5, monocyte, NF-κB

Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes, yet the mechanisms are not completely understood. Here, we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control. miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics. LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels. Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice. Conversely, lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration, reduced body weight, and improved glucose metabolism in db/db mice. And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE−/− mice. Both OPG and KLF5 were targets of miR-145. miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5. miR-145 also suppressed NF-κB activation by targeting OPG and KLF5. Our findings provide an association of the environment with the progress of metabolic disorders. Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.

Volume 12, Issue 2
February 2020