miR-145 improves metabolic inflammatory disease through multiple pathways  

作　　者：Min He Nan Wu Man Cheong Leong Weiwei Zhang Zi Ye Rumei Li Jinyang Huang Zhaoyun Zhang Lianxi Li Xiao Yao Wenbai Zhou Naijia Liu Zhihong Yang Xuehong Dong Yintao Li Lili Chen Qin Li Xuanchun Wang Jie Wen Xiaolong Zhao Bin Lu Yehong Yang Qinghua Wang Renming Hu 

机构地区：[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.Michaers Hospital,University of Toronto,Ontario,Canada

出　　处：《Journal of Molecular Cell Biology》2020年第2期152-162,共11页分子细胞生物学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(81270902,81381220308,and 30230380).

摘　　要：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.

关 键 词：type 2 diabetes OSTEOPROTEGERIN Kruppel-like factor 5 MONOCYTE NF-ΚB 

分 类 号：R589[医药卫生—内分泌]