TGF-β1 epigenetically modifies Thy-1 expression in primary lung fibroblasts

American Journal of Physiology. Cell Physiology
Wendy A NeveuViranuj Sueblinvong

Abstract

Idiopathic pulmonary fibrosis is a progressive lung disease that increases in incidence with age. We identified a profibrotic lung phenotype in aging mice characterized by an increase in the number of fibroblasts lacking the expression of thymocyte differentiation antigen 1 (Thy-1) and an increase in transforming growth factor (TGF)-β1 expression. It has been shown that Thy-1 expression can be epigenetically modified. Lung fibroblasts (PLFs) were treated with TGF-β1 ± DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-AZA) and analyzed for Thy-1 gene and protein expression, DNMT protein expression, and activity. α-Smooth muscle actin (α-SMA) and collagen type 1 (Col1A1) gene and protein expression was assessed. PLFs were transfected with DNMT1 silencing RNA ± TGF-β1. TGF-β1 inhibited Thy-1 gene and protein expression in PLFs, and cotreatment with 5-AZA ameliorated this effect and appeared to inhibit DNMT1 activation. TGF-β1 induced Thy-1 promoter methylation as assessed by quantitative methyl PCR. Treatment with 5-AZA attenuated TGF-β1-induced Col1A1 gene and protein expression and α-SMA gene expression (but not α-SMA protein expression). Inhibiting DNMT1 with silencing RNA attenuated TGF-β1-induced DNMT activity ...Continue Reading

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Citations

Oct 31, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E'Lissa M FloresRichard P Phipps
Mar 1, 2019·Environmental Toxicology·Na ZhangHuifang Yang
Apr 15, 2018·Stem Cell Research & Therapy·Feng ZhangYan He
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May 4, 2020·International Immunopharmacology·Chun-Hao LuMing-Ling Kuo
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Sep 22, 2021·Advances in Wound Care·Artem A TrotsyukGeoffrey C Gurtner
Jul 23, 2020·Minerva medica·Xiaoping LiJames S Hagood

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