Quantitative proteomics reveals the mechanism of endoplasmic reticulum stress-mediated pulmonary fibrosis in mice
Heng Li,
Jin Wang,
Ziling Li,
Zhidong Wu,
Yan Zhang,
Lingjia Kong,
Qingqing Yang,
Dong Wang,
He Shi,
Guozheng Shen,
Shuang Zou,
Wenqing Zhu,
Kaiyuan Fan,
Zhongwei Xu
Affiliations
Heng Li
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Jin Wang
Department of Clinical Laboratory, Tianjin Third Central Hospital, Tianjin, 300170, People's Republic of China
Ziling Li
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Zhidong Wu
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Yan Zhang
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Lingjia Kong
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Qingqing Yang
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Dong Wang
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
He Shi
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Guozheng Shen
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Shuang Zou
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China
Wenqing Zhu
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China; Corresponding author. Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China.
Kaiyuan Fan
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China; Corresponding author. Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China.
Zhongwei Xu
Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin, 300309, People's Republic of China; Tianjin key laboratory for prevention and control of occupational and environmental hazards, 300309, People's Republic of China; Corresponding author. Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, People's Republic of China. Tianjin key laboratory for preventing and controlling occupational and environmental hazards, 300309, People's Republic of China.
Pulmonary fibrosis is a progressive disease that can lead to respiratory failure. Many types of cells are involved in the progression of pulmonary fibrosis. This study utilized quantitative proteomics to investigate the mechanism of TGF-β-induced fibrosis-like changes in mouse epithelial cells. Our findings revealed that TGF-β significantly impacted biological processes related to the endoplasmic reticulum, mitochondrion, and ribonucleoprotein complex. Pull-down assay coupled with proteomics identified 114 proteins that may directly interact with TGF-β, and their functions were related to mitochondria, translation, ubiquitin ligase conjugation, mRNA processing, and actin binding. Among them, 17 molecules were also found in different expression proteins (DEPs) of quantitative proteomic, such as H1F0, MED21, SDF2L1, DAD1, and TMX1. Additionally, TGF-β decreased the folded structure and the number of ribosomes in the endoplasmic reticulum and increased the expression of key proteins in the unfolded protein response, including HRD1, PERK, and ERN1. Overall, our study suggested that TGF-β induced fibrotic changes in mouse lung epithelial cells by ER stress and initiated the unfolded protein response through the PRKCSH/IRE1 and PERK/GADD34/CHOP signaling pathways.
