MicroRNA-186 promotes macrophage lipid accumulation and secretion of pro-inflammatory cytokines by targeting cystathionine γ-lyase in THP-1 macrophages
Authors: Chao-Ke Tang
Yan Yao
Wei Xie
Zhen-Wang Zhao
Xin Zhang
Liang Li
Gang Lan
Hai-Peng Chen
Zong-Bao Wang
Xi-Long Zheng
Journal: Atherosclerosis (2016)
Discipline: CLINICAL MEDICINE
Keywords: Cystathionine γ-Lyase; Hydrogen sulfide; Lipoprotein lipase; miR-186.
Affiliations: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China; Department of Biochemistry and Molecular Biology, School of Pharmacy and Life Science, University of South China, Hengyang, Hunan, 421001, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China., Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Libin Cardiovascular Institute of Alberta, University of Calgary, Health Sciences Center, 3330 Hospital Dr.NW, Calgary, Alberta, T2N 4N1, Canada., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China; Department of Biochemistry and Molecular Biology, School of Pharmacy and Life Science, University of South China, Hengyang, Hunan, 421001, China. Electronic address: ., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China. Electronic address: .

Abstract:  Background and aims: Several studies suggest that cardiomyocyte-enriched miR-186 is involved in cardiac injury and myocardial infarction, and also plays an important role in atherosclerotic diseases, but the underlying mechanism is unknown. Cystathionine-γ-lyase (CSE) is the predominant enzyme to produce H2S in the cardiovascular system. Here, miR-186 was identified to bind to the 3'UTR of CSE. In this study, we aimed at exploring whether miR-186 affects lipid accumulation and secretion of pro-inflammatory cytokines by targeting CSE and its underlying mechanism in human THP-1 macrophages and peripheral blood monocyte-derived macrophages (PBMDM). PBMDM just as a control group for the comparison with the THP-1 macrophages. Methods: MiR-186 target genes, CSE 3'UTR sequence and free energy were predicted and analyzed by bioinformatics analyses and dual-luciferase reporter assays. The expression of CSE mRNA and protein were measured by real-time quantitative PCR and western blot analyses. The lipid accumulation in THP-1 macrophages was detected by high performance liquid chromatography (HPLC). The effects of miR-186 on secretion of IL-6, IL-1β and TNF-α were examined by ELISA. Endogenous H2S was detected by spectrophotometry. Using small interfering RNA (siRNA) approach to decrease the expression of CSE protein and mRNA. Results: We found that miR-186 directly inhibited CSE protein and mRNA expression through targeting CSE 3'UTR by bioinformatics analyses and dual-luciferase reporter assays. HPLC assays showed that miR-186 increased the lipid accumulation in human THP-1 macrophages. We also showed that miR-186 enhanced secretion of pro-inflammatory cytokines in human THP-1 macrophages. Using siRNA approach, we found that CSE siRNA could inhibit the miR-186 inhibitor-induced decrease in the expression of LPL protein and mRNA in human THP-1 macrophages, which was accompanied a decrease in the level of H2S. Conclusions: MicroRNA-186 promotes macrophage lipid accumulation and pro-inflammatory cytokine secretion by targeting cystathionine γ-lyase in THP-1 macrophages. 

Retracted: No

PubPeer comments:
 Figure 5. This doesn t look too good. This paper is part of a growing number of papers by the same senior author on topics related to lipid metabolism and atherosclerosis that contain questionable data and images. ![file] , 
 Copy pasted from https: doi.org 10.1016 j.atherosclerosis.2021.06.923 :  Editorial expression of concern: u201cMicroRNA-186 promotes macrophage lipid accumulation and secretion of pro-inflammatory cytokines by targeting cystathionine u03b3-lyase in THP-1 macrophagesu201d [Atherosclerosis Volume 250, July 2016, Pages 122u2013132]. Published:June 25, 2021. The Editors of Atherosclerosis are issuing an expression of concern to alert readers that credible concerns have been raised regarding the quality of some data in the article above. See also https: retractionwatch.com 2021 07 09 they-seem-to-mean-business-cardiology-journal-flags-papers-cited-hundreds-of-times ,