Vitamin D attenuates TGF-beta 1-induced lung fibroblast proliferation and migration through repression of RasGRP3

doi:10.32604/biocell.2023.027763

科研成果详情

题名	Vitamin D attenuates TGF-beta 1-induced lung fibroblast proliferation and migration through repression of RasGRP3
作者	Hu, Guanqiong1; Huang, Risheng 2; Lu, Luelue 1; Pan, Qinshi3; Chen, Xiaoxin1
发表日期	2023
发表期刊	BIOCELL 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Lung fibrosis RasGRP3 TGF-131 Vitamin D
其他关键词	TGF-BETA ; D-RECEPTOR ; FIBROSIS ; INHIBITION ; EXPRESSION ; CELLS
摘要	Background: Transforming growth factor-131 (TGF-131) 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-131 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-131 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-131 signaling in lung fibroblast activation. Bioinformatic analysis was performed to identify TGF-131 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-131-treated lung fibroblasts and lung tissues from IPF patients relative to healthy controls. Our data confirmed the upregulation of RasGRP3 by TGF-131 in human MRC5 lung fibroblasts. Overexpression of RasGRP3 enhanced MRC5 cell proliferation and migration. Knockdown of RasGRP3 blocked TGF-131-induced MRC5 proliferation and migration. Vitamin D abolished TGF-131-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-131-induced lung fibroblast activation by repressing RasGRP3 transcription.
资助项目	Basic Scientific Research Project of Wenzhou of China[Y20210068];Ministry of Education of China[202101160012];
出版者	TECH SCIENCE PRESS
ISSN	0327-9545
EISSN	1667-5746
卷号	47 期号:6 页码:1243-1251
DOI	10.32604/biocell.2023.027763
页数	9
WOS类目	Biology
WOS研究方向	Life Sciences & Biomedicine - Other Topics
WOS记录号	WOS:000989073300001
收录类别	SCIE ; SCOPUS
在线发表日期	2023-05
URL	查看原文
SCOPUSEID	2-s2.0-85161959938
通讯作者地址	[Chen, Xiaoxin]No. 23 Ward of Nursing Department,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Cell Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180170
专题	附属第一医院其他_定理临床学院（温州市中心医院）
通讯作者	Chen, Xiaoxin
作者单位	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
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Hu, Guanqiong,Huang, Risheng,Lu, Luelue,et al. Vitamin D attenuates TGF-beta 1-induced lung fibroblast proliferation and migration through repression of RasGRP3[J]. BIOCELL,2023,47(6):1243-1251.
APA	Hu, Guanqiong, Huang, Risheng, Lu, Luelue, Pan, Qinshi, & Chen, Xiaoxin. (2023). Vitamin D attenuates TGF-beta 1-induced lung fibroblast proliferation and migration through repression of RasGRP3. BIOCELL, 47(6), 1243-1251.
MLA	Hu, Guanqiong,et al."Vitamin D attenuates TGF-beta 1-induced lung fibroblast proliferation and migration through repression of RasGRP3".BIOCELL 47.6(2023):1243-1251.