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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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Autores principales: Xiang, Di, Jiang, Lei, Yuan, Qiong, Yu, Yang, Liu, Ruiming, Chen, Meiting, Kuai, Zheng, Zhang, Wendy, Yang, Fan, Wu, Tingting, He, Zhiyu, Ke, Zuhui, Hong, Wanzi, He, Pengcheng, Tan, Ning, Sun, Yeying, Shi, Zhen, Wei, Xuebiao, Luo, Jianfang, Tan, Xiaoqiu, Huo, Yuqing, Qin, Gangjian, Zhang, Chunxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAAS 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10325668/
https://www.ncbi.nlm.nih.gov/pubmed/37426471
http://dx.doi.org/10.34133/research.0187
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author Xiang, Di
Jiang, Lei
Yuan, Qiong
Yu, Yang
Liu, Ruiming
Chen, Meiting
Kuai, Zheng
Zhang, Wendy
Yang, Fan
Wu, Tingting
He, Zhiyu
Ke, Zuhui
Hong, Wanzi
He, Pengcheng
Tan, Ning
Sun, Yeying
Shi, Zhen
Wei, Xuebiao
Luo, Jianfang
Tan, Xiaoqiu
Huo, Yuqing
Qin, Gangjian
Zhang, Chunxiang
author_facet Xiang, Di
Jiang, Lei
Yuan, Qiong
Yu, Yang
Liu, Ruiming
Chen, Meiting
Kuai, Zheng
Zhang, Wendy
Yang, Fan
Wu, Tingting
He, Zhiyu
Ke, Zuhui
Hong, Wanzi
He, Pengcheng
Tan, Ning
Sun, Yeying
Shi, Zhen
Wei, Xuebiao
Luo, Jianfang
Tan, Xiaoqiu
Huo, Yuqing
Qin, Gangjian
Zhang, Chunxiang
author_sort Xiang, Di
collection PubMed
description 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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spelling pubmed-103256682023-07-07 Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis Xiang, Di Jiang, Lei Yuan, Qiong Yu, Yang Liu, Ruiming Chen, Meiting Kuai, Zheng Zhang, Wendy Yang, Fan Wu, Tingting He, Zhiyu Ke, Zuhui Hong, Wanzi He, Pengcheng Tan, Ning Sun, Yeying Shi, Zhen Wei, Xuebiao Luo, Jianfang Tan, Xiaoqiu Huo, Yuqing Qin, Gangjian Zhang, Chunxiang Research (Wash D C) Research Article 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. AAAS 2023-07-06 /pmc/articles/PMC10325668/ /pubmed/37426471 http://dx.doi.org/10.34133/research.0187 Text en Copyright © 2023 Di Xiang et al. https://creativecommons.org/licenses/by/4.0/Exclusive licensee Science and Technology Review Publishing House. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Xiang, Di
Jiang, Lei
Yuan, Qiong
Yu, Yang
Liu, Ruiming
Chen, Meiting
Kuai, Zheng
Zhang, Wendy
Yang, Fan
Wu, Tingting
He, Zhiyu
Ke, Zuhui
Hong, Wanzi
He, Pengcheng
Tan, Ning
Sun, Yeying
Shi, Zhen
Wei, Xuebiao
Luo, Jianfang
Tan, Xiaoqiu
Huo, Yuqing
Qin, Gangjian
Zhang, Chunxiang
Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis
title Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis
title_full Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis
title_fullStr Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis
title_full_unstemmed Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis
title_short Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis
title_sort leukocyte-specific morrbid promotes leukocyte differentiation and atherogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10325668/
https://www.ncbi.nlm.nih.gov/pubmed/37426471
http://dx.doi.org/10.34133/research.0187
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