Open Access
ARTICLE
Vitamin D attenuates TGF-β1-induced lung fibroblast proliferation and migration through repression of RasGRP3
GUANQIONG HU1, RISHENG HUANG2, LUELUE LU1, QINSHI PAN3, XIAOXIN CHEN1,*
1 No. 23 Ward of Nursing Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
2 Department of Thoracic Surgery, Wenzhou Central Hospital, Dingli Clinical College of Wenzhou Medical University, Wenzhou, China
3 Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
* Corresponding Author: Xiaoxin Chen,
(This article belongs to the Special Issue: Biochemical and Epigenetics Changes in Health and Disease)
BIOCELL 2023, 47(6), 1243-1251. https://doi.org/10.32604/biocell.2023.027763
Received 14 November 2022; Accepted 31 January 2023; Issue published 19 May 2023
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusion: In conclusion, vitamin D antagonizes TGF-β1-induced lung
fibroblast activation by repressing RasGRP3 transcription.
Keywords
Cite This Article
HU, G., HUANG, R., LU, L., PAN, Q., CHEN, X. (2023). Vitamin D attenuates TGF-β1-induced lung fibroblast proliferation and migration through repression of
RasGRP3.
BIOCELL, 47(6), 1243–1251. https://doi.org/10.32604/biocell.2023.027763