DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation

doi:10.1038/s41536-023-00306-2

	DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation
	Zhao, Chuanrong ; Yang, Qianru ; Tang, Runze ; Li, Wang ; Wang, Jin ; Yang, Fangfang ; Zhao, Jianan ; Zhu, Juanjuan ; Pang, Wei ; Li N(李宁)
刊名	NPJ REGENERATIVE MEDICINE ; 1
	2023-06-08
卷号	8 页码:29
DOI	10.1038/s41536-023-00306-2
英文摘要	Healing of the cutaneous wound requires macrophage recruitment at the sites of injury, where chemotactic migration of macrophages toward the wound is regulated by local inflammation. Recent studies suggest a positive contribution of DNA methyltransferase 1 (Dnmt1) to macrophage pro-informatory responses; however, its role in regulating macrophage motility remains unknown. In this study, myeloid-specific depletion of Dnmt1 in mice promoted cutaneous wound healing and de-suppressed the lipopolysaccharides (LPS)-inhibited macrophage motility. Dnmt1 inhibition in macrophages eliminated the LPS-stimulated changes in cellular mechanical properties in terms of elasticity and viscoelasticity. LPS increased the cellular accumulation of cholesterol in a Dnmt1-depedent manner; cholesterol content determined cellular stiffness and motility. Lipidomic analysis indicated that Dnmt1 inhibition altered the cellular lipid homeostasis, probably through down-regulating the expression of cluster of differentiation 36 CD36 (facilitating lipid influx) and up-regulating the expression of ATP-binding cassette transporter ABCA1 (mediating lipid efflux) and sterol O-acyltransferase 1 SOAT1 (also named ACAT1, catalyzing the esterification of cholesterol). Our study revealed a Dnmt1-dependent epigenetic mechanism in the control of macrophage mechanical properties and the related chemotactic motility, indicating Dnmt1 as both a marker of diseases and a potential target of therapeutic intervention for wound healing.
分类号	一类
WOS研究方向	Cell & Tissue Engineering ; Engineering, Biomedical
语种	英语
WOS记录号	WOS:001002728000001
资助机构	Ministry of Science and Technology [2022YFC2704300] ; National Natural Science Foundation of China [82270419, 81974052, 81921001, 32171143, 11732001, 32201071, 32071145]
其他责任者	Yao, WJ ; Zhou, J (corresponding author), Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China. ; Zhou, J (corresponding author), Peking Univ, State Key Lab Vasc Homeostasis & Remodeling, Beijing 100191, Peoples R China. ; Zhou, J (corresponding author), Peking Univ, Natl Hlth Commiss Key Lab Cardiovasc Mol Biol & Re, Beijing Key Lab Cardiovasc Receptors Res, Beijing 100191, Peoples R China.
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/92378]
专题	力学研究所_国家微重力实验室
作者单位	1.{Tian Xiao Yu} Chinese Univ Hong Kong Heart & Vasc Inst CUHK Shenzhen Res Inst Sch Biomed Sci Hong Kong 999077 Peoples R China 2.{Zhang Xu} Tianjin Med Univ Prov & Minist Cosponsored Collaborat Innovat Ctr M Ctr Cardiovasc Dis Res Ctr Basic Med SciDept Physiol & Pathophysiol Tianjin 300070 Peoples R China 3.{Li Wang, Li Ning} Chinese Acad Sci Inst Mech Key Lab Micrograv Nat Micrograv Lab Beijing 100190 Peoples R China 4.{Li Wang, Li Ning} Chinese Acad Sci Inst Mech Ctr Biomech & Bioengn Beijing Key Lab Engn Construction & Mechanobiol Beijing 100190 Peoples R China 5.{Li Wang, Li Ning} Univ Chinese Acad Sci Sch Engn Sci Beijing 100190 Peoples R China 6.{Zhao Chuanrong, Yang Qianru, Tang Runze, Wang Jin, Yang Fangfang, Zhao Jianan, Zhu Juanjuan, Zhou Jing} Peking Univ Natl Hlth Commiss Key Lab Cardiovasc Mol Biol & Re Beijing Key Lab Cardiovasc Receptors Res Beijing 100191 Peoples R China 7.{Zhao Chuanrong, Yang Qianru, Tang Runze, Wang Jin, Yang Fangfang, Zhao Jianan, Zhu Juanjuan, Zhou Jing} Peking Univ State Key Lab Vasc Homeostasis & Remodeling Beijing 100191 Peoples R China 8.{Zhao Chuanrong, Yang Qianru, Tang Runze, Wang Jin, Yang Fangfang, Zhao Jianan, Zhu Juanjuan, Pang Wei, Yao Weijuan, Zhou Jing} Peking Univ Sch Basic Med Sci Dept Physiol & Pathophysiol Beijing 100191 Peoples R China
推荐引用方式 GB/T 7714	Zhao, Chuanrong,Yang, Qianru,Tang, Runze,et al. DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation[J]. NPJ REGENERATIVE MEDICINE, 1,2023,8:29.
APA	Zhao, Chuanrong.,Yang, Qianru.,Tang, Runze.,Li, Wang.,Wang, Jin.,...&Zhou, Jing.(2023).DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation.NPJ REGENERATIVE MEDICINE,8,29.
MLA	Zhao, Chuanrong,et al."DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation".NPJ REGENERATIVE MEDICINE 8(2023):29.