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

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

PROVIDER: PRJNA976933 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24753655_1.fastq.gz	Fastqsanger.gz
	SRR24753655_2.fastq.gz	Fastqsanger.gz
	SRR24753656_1.fastq.gz	Fastqsanger.gz
	SRR24753656_2.fastq.gz	Fastqsanger.gz
	SRR24753657_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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

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