Vitamin D3 alleviates pulmonary fibrosis by regulating the MAPK pathway via targeting PSAT1 expression in vivo and in vitro

作者：Wenxiang Zhu, Qi Ding, Lu Wang, Gonghao Xu, Yirui Diao, Sihao Qu, Sheng Chen, Yuanyuan Shi · 发表于：International Immunopharmacology · 年份：2021 · DOI：10.1016/j.intimp.2021.108212 · 被引用次数：39 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Occupational and environmental lung diseases、Medical Imaging and Pathology Studies

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic lung disease. However, there are insufficient drugs available for IPF treatment, and the currently used drugs are accompanied by many adverse reactions. Deficiency of vitamin D3 (VD3) in the development of IPF and the potential role of VD3 in the treatment of IPF have attracted increasing attention. In vivo experimental results showed that VD3 could increase the survival rate in bleomycin (BLM)-induced models, relieve lung inflammation, reduce hydroxyproline content, and inhibit collagen deposition and cell apoptosis. We further performed proteomics analysis and screened 251 target proteins that reflect VD3 intervention in BLM-induced animal models. These target proteins were involved in acute inflammation, oxidative stress, antioxidant activity and extracellular matrix binding. Combined with the comprehensive analysis of clinical samples, PSAT1 was screened out as a candidate target related to IPF disease and VD3 treatment. Through further computational analysis, the MAPK signaling pathway was considered to be the most probable candidate pathway for VD3 function targeting IPF. In in vivo experiments, VD3 inhibited BLM-induced expression of PSAT1 and phosphorylation of p38 and ERK1/2 in mouse lung tissue. The experiments of cell proliferation and western blot confirmed that VD3 inhibited the expression of PSAT1 and the activation of the mitogen-activated protein kinase (MAPK) pathway in human pulmonary fi...