Methyl-CpG-binding protein 2 mediates antifibrotic effects in scleroderma fibroblasts

Annals of the Rheumatic Diseases
Ye HeAmr H Sawalha

Abstract

Emerging evidence supports a role for epigenetic regulation in the pathogenesis of scleroderma (SSc). We aimed to assess the role of methyl-CpG-binding protein 2 (MeCP2), a key epigenetic regulator, in fibroblast activation and fibrosis in SSc. Dermal fibroblasts were isolated from patients with diffuse cutaneous SSc (dcSSc) and from healthy controls. MeCP2 expression was measured by qPCR and western blot. Myofibroblast differentiation was evaluated by gel contraction assay in vitro. Fibroblast proliferation was analysed by ki67 immunofluorescence staining. A wound healing assay in vitro was used to determine fibroblast migration rates. RNA-seq was performed with and without MeCP2 knockdown in dcSSc to identify MeCP2-regulated genes. The expression of MeCP2 and its targets were modulated by siRNA or plasmid. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-MeCP2 antibody was performed to assess MeCP2 binding sites within MeCP2-regulated genes. Elevated expression of MeCP2 was detected in dcSSc fibroblasts compared with normal fibroblasts. Overexpressing MeCP2 in normal fibroblasts suppressed myofibroblast differentiation, fibroblast proliferation and fibroblast migration. RNA-seq in MeCP2-deficient dcS...Continue Reading

Citations

Aug 25, 2019·Cells·Marzena CiechomskaWlodzimierz Maslinski
Mar 3, 2020·Journal of Cellular Biochemistry·Zheyi XiangYan Y Sanders
Dec 11, 2019·The Journal of Comparative Neurology·Kristi A StreeterDavid D Fuller
Jun 24, 2018·Nature Reviews. Rheumatology·Isobel Leake
Dec 10, 2019·Current Rheumatology Reports·Pei-Suen Tsou
Sep 23, 2020·Current Rheumatology Reports·Hanlin YinQingran Yan

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