首页|Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis

Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis

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Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(IncRNAs)are a group of protein expression regulators;however,the roles of monocyte-IncRNAs in macrophage differentiation and its related vascular diseases are still unclear.The study aims to investigate whether the novel leukocyte-specific IncRNA Morrbid could regulate macrophage differentiation and atherogenesis.We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis.In cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation.The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown.Moreover,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation.The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice.We identified that P13-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation.To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in mice.The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice.The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.

Di Xiang、Lei Jiang、Qiong Yuan、Yang Yu、Ruiming Liu、Meiting Chen、Zheng Kuai、Wendy Zhang、Fan Yang、Tingting Wu、Zhiyu He、Zuhui Ke、Wanzi Hong、Pengcheng He、Ning Tan、Yeying Sun、Zhen Shi、Xuebiao Wei、Jianfang Luo、Xiaoqiu Tan、Yuqing Huo、Gangjian Qin、Chunxiang Zhang

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Department of Cardiology,Key Laboratory of Medical Electrophysiology,Ministry of Education,Institute of Cardiovascular Research,The Affiliated Hospital of Southwest Medical University,Southwest Medical University,Luzhou,Sichuan 646000,China

Department of Biomedical Engineering,School of Medicine,The University of Alabama at Birmingham,Birmingham,AL 35233,USA

Department of Cardiology,Guangdong Cardiovascular Institute,Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention,Guangdong Provincial Institute of Geriatric Medicine,Guangdong General Hospital,Guangdong Academy of Medical Sciences,Guangzhou,Guangdong 510100,China

Vascular Biology Center,Medical College of Georgia,Augusta University,Augusta,GA 30912,USA

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaCentral Government Guides Local Science and Technology Development ProjectSichuan Science and Technology ProgramSichuan Science and Technology ProgramStartup Research Fund of Southwest Medical UniversityStartup fund from the University of Alabama at Birmingham

8203000781670398916391022022ZYD00572022YFS05782022YFS061400040155

2024

10.34133/research.0187

研究(英文)

研究(英文)

CSTPCD
ISSN：
年,卷(期)：2024.2024(2)
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