DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation
文献类型：期刊论文
| Author | Zhao, Chuanrong; Yang, Qianru; Tang, Runze; Li, Wang ; Wang, Jin; Yang, Fangfang; Zhao, Jianan; Zhu, Juanjuan; Pang, Wei; Li N(李宁)
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| Source | NPJ REGENERATIVE MEDICINE
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| Issued Date | 2023-06-08 |
| Volume | 8Issue:1Pages:29 |
| DOI | 10.1038/s41536-023-00306-2 |
| English Abstract | 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. |
| Classification | 一类 |
| WOS Research Area | Cell & Tissue Engineering ; Engineering, Biomedical |
| Language | 英语 |
| WOS ID | WOS:001002728000001 |
| Funding Organization | Ministry of Science and Technology [2022YFC2704300] ; National Natural Science Foundation of China [82270419, 81974052, 81921001, 32171143, 11732001, 32201071, 32071145] |
| Other responsible | 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. |
| 源URL | [http://dspace.imech.ac.cn/handle/311007/92378]  |
| Collection | 力学研究所_国家微重力实验室 |
| Affiliation | 1.{Li Wang, Li Ning} Chinese Acad Sci Inst Mech Ctr Biomech & Bioengn Beijing Key Lab Engn Construction & Mechanobiol Beijing 100190 Peoples R China 2.{Li Wang, Li Ning} Chinese Acad Sci Inst Mech Key Lab Micrograv Nat Micrograv Lab Beijing 100190 Peoples R China 3.{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 4.{Tian Xiao Yu} Chinese Univ Hong Kong Heart & Vasc Inst CUHK Shenzhen Res Inst Sch Biomed Sci Hong Kong 999077 Peoples R China 5.{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 6.{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 7.{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 8.{Li Wang, Li Ning} Univ Chinese Acad Sci Sch Engn Sci Beijing 100190 Peoples R China |
| Recommended Citation 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,2023,8(1):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(1),29. |
| MLA | Zhao, Chuanrong,et al."DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation".NPJ REGENERATIVE MEDICINE 8.1(2023):29. |
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来源：力学研究所
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