MiR-375 silencing attenuates pro-inflammatory macrophage response and foam cell formation by targeting KLF4

Journal Article · Mon Mar 15 04:00:00 EDT 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2021.112507· OSTI ID:23195349

Qiu, Yanyan; Xu, Jinyi; Yang, Lihong; Zhao, Guihua; Ding, Jing ^[1]; others, and

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1. Department of Cardio-Pulmonary Function, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, 450003 (China)

Macrophage mediated inflammation and foam cell formation play crucial roles in the development of atherosclerosis. MiR-375 is a small noncoding RNA that significantly implicated in multiple tumor regulation and has been emerged as a novel biomarker for type 2 diabetes. However, the exact role of miR-375 on macrophage activation remains unknown. In the present study, we observed that miR-375 expression showed an up-regulated expression in atherosclerotic aortas, as well as in bone marrow derived macrophages (BMDMs) and mouse peritoneal macrophages (MPMs) isolated from ApoE deficiency mice and was gradually increased followed the Ox-LDL treated time. Functionally, miR-375 inhibition significantly decreased foam cell formation accompanied by up-regulated genes expression involved in cholesterol efflux but reduced genes expression implicated in cholesterol influx. Moreover, miR-375 silencing increased resolving M2 macrophage but reduced pro-inflammatory M1 macrophage markers expression. Such above effects can be reversed by miR-375 overexpression. Mechanistically, we noticed that miR-375 knockdown promoted KLF4 expression which was required for the ameliorated effect of miR-375 silencing on macrophage activation. Importantly, the consistent results in mRNA expression of M1 and M2 markers were observed in vivo, and miR-375{sup −/−}ApoE{sup −/−} mice significant decreased atherosclerotic lesions in the whole aorta and aortic sinus. Taken together, these evidences suggested that miR-375 knockdown attenuated macrophage activation partially through activation of KLF4-dependent mechanism.

• OSTI ID: 23195349
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 400; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AORTA
ARTERIOSCLEROSIS
BIOLOGICAL MARKERS
BONE MARROW
CHOLESTEROL
GENE REGULATION
IN VIVO
INFLAMMATION
INHIBITION
MACROPHAGES
MESSENGER-RNA
MICE
NEOPLASMS
SINUSES