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
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
ISSN0327-9545
EISSN1667-5746
卷号47期号:6页码:1243-1251
DOI10.32604/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
SCOPUSEID2-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.

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