@Article{biocell.2023.027763,
AUTHOR = {GUANQIONG HU, RISHENG HUANG, LUELUE LU, QINSHI PAN, XIAOXIN CHEN},
TITLE = {Vitamin D attenuates TGF-β1-induced lung fibroblast proliferation and migration through repression of <i>RasGRP3</i>},
JOURNAL = {BIOCELL},
VOLUME = {47},
YEAR = {2023},
NUMBER = {6},
PAGES = {1243--1251},
URL = {http://www.techscience.com/biocell/v47n6/52795},
ISSN = {1667-5746},
ABSTRACT = {<b>Background:</b> Transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine that plays a central role in the
pathogenesis of idiopathic pulmonary fibrosis (IPF). While previous studies have revealed a cross-talk between vitamin D
and TGF-β1 signaling, it is still unclear how they interact with each other to regulate the progression of IPF. <b>Methods:</b> In
this work, we searched for a novel mediator of TGF-β1 activity in lung fibroblasts and examined its regulation by vitamin
D. In addition, we investigated the mechanism underlying the interaction between vitamin D and TGF-β1 signaling in
lung fibroblast activation. Bioinformatic analysis was performed to identify TGF-β1 downstream target genes.
Knockdown and overexpression expression experiments were conducted to determine gene function in the regulation
of lung fibroblast proliferation and migration. <b>Results: </b>Analysis of publicly available datasets revealed that RAS
guanyl releasing protein 3 (RasGRP3) was upregulated in TGF-β1-treated lung fibroblasts and lung tissues from IPF
patients relative to healthy controls. Our data confirmed the upregulation of RasGRP3 by TGF-β1 in human MRC5
lung fibroblasts. Overexpression of RasGRP3 enhanced MRC5 cell proliferation and migration. Knockdown of
RasGRP3 blocked TGF-β1-induced MRC5 proliferation and migration. Vitamin D abolished TGF-β1-induced
RasGRP3 upregulation, which was reversed by inhibition of the vitamin D receptor (VDR). Mechanistically, vitamin
D promoted VDR enrichment and prevented mothers against decapentaplegic homolog (SMAD) 2 and 3 occupancy
at the promoter of RasGRP3. Additionally, overexpression of RasGRP3 reversed the suppressive effect of vitamin D
on MRC5 cell proliferation and migration. <b>Conclusion: </b>In conclusion, vitamin D antagonizes TGF-β1-induced lung
fibroblast activation by repressing RasGRP3 transcription.},
DOI = {10.32604/biocell.2023.027763}
}