Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis
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 (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage diff...
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Published in | Research (Washington) Vol. 6; p. 0187 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
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01.01.2023
American Association for the Advancement of Science (AAAS) |
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Abstract | 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 (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA 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 PI3-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. |
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AbstractList | 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 (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA 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 PI3-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. |
Author | He, Pengcheng Chen, Meiting Shi, Zhen Wei, Xuebiao Yuan, Qiong Kuai, Zheng Ke, Zuhui Jiang, Lei Liu, Ruiming Luo, Jianfang Tan, Xiaoqiu Huo, Yuqing Zhang, Wendy He, Zhiyu Hong, Wanzi Qin, Gangjian Xiang, Di Yu, Yang Wu, Tingting Sun, Yeying Yang, Fan Tan, Ning Zhang, Chunxiang |
AuthorAffiliation | 4 Vascular Biology Center, Medical College of Georgia , Augusta University , Augusta, GA 30912, USA 1 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 2 Department of Biomedical Engineering, School of Medicine , The University of Alabama at Birmingham , Birmingham, AL 35233, USA 3 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 |
AuthorAffiliation_xml | – name: 2 Department of Biomedical Engineering, School of Medicine , The University of Alabama at Birmingham , Birmingham, AL 35233, USA – name: 3 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 – name: 4 Vascular Biology Center, Medical College of Georgia , Augusta University , Augusta, GA 30912, USA – name: 1 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 |
Author_xml | – sequence: 1 givenname: Di surname: Xiang fullname: Xiang, Di organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 2 givenname: Lei surname: Jiang fullname: Jiang, Lei organization: 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 – sequence: 3 givenname: Qiong surname: Yuan fullname: Yuan, Qiong organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 4 givenname: Yang surname: Yu fullname: Yu, Yang organization: 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 – sequence: 5 givenname: Ruiming surname: Liu fullname: Liu, Ruiming organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 6 givenname: Meiting surname: Chen fullname: Chen, Meiting organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 7 givenname: Zheng surname: Kuai fullname: Kuai, Zheng organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 8 givenname: Wendy surname: Zhang fullname: Zhang, Wendy organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 9 givenname: Fan surname: Yang fullname: Yang, Fan organization: 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 – sequence: 10 givenname: Tingting surname: Wu fullname: Wu, Tingting organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 11 givenname: Zhiyu surname: He fullname: He, Zhiyu organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 12 givenname: Zuhui surname: Ke fullname: Ke, Zuhui organization: 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 – sequence: 13 givenname: Wanzi surname: Hong fullname: Hong, Wanzi organization: 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 – sequence: 14 givenname: Pengcheng surname: He fullname: He, Pengcheng organization: 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 – sequence: 15 givenname: Ning surname: Tan fullname: Tan, Ning organization: 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 – sequence: 16 givenname: Yeying surname: Sun fullname: Sun, Yeying organization: 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 – sequence: 17 givenname: Zhen surname: Shi fullname: Shi, Zhen organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 18 givenname: Xuebiao surname: Wei fullname: Wei, Xuebiao organization: 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 – sequence: 19 givenname: Jianfang surname: Luo fullname: Luo, Jianfang organization: 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 – sequence: 20 givenname: Xiaoqiu surname: Tan fullname: Tan, Xiaoqiu organization: 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 – sequence: 21 givenname: Yuqing surname: Huo fullname: Huo, Yuqing organization: Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA – sequence: 22 givenname: Gangjian surname: Qin fullname: Qin, Gangjian organization: Department of Biomedical Engineering, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35233, USA – sequence: 23 givenname: Chunxiang orcidid: 0000-0003-3308-0265 surname: Zhang fullname: Zhang, Chunxiang organization: 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 |
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Title | Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis |
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