miR-145 improves metabolic inflammatory disease through multiple pathways

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2020,（2）
• 页码范围: 152-162
• 页数: 11页
• 语种: 英文
• DOI: 10.1093/jmcb/mjz015

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 miR143/145 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.