Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice

Keyun Shi; Jianzhong Jiang; Tieliang Ma; Jing Xie; Lirong Duan; Ruhua Chen; Ping Song; Zhixin Yu; Chao Liu; Qin Zhu; Jinxu Zheng

doi:10.1016/j.resp.2013.09.011

Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice

Respir Physiol Neurobiol. 2014 Jan 1:190:113-7. doi: 10.1016/j.resp.2013.09.011. Epub 2013 Oct 17.

Authors

Keyun Shi¹, Jianzhong Jiang, Tieliang Ma, Jing Xie, Lirong Duan, Ruhua Chen, Ping Song, Zhixin Yu, Chao Liu, Qin Zhu, Jinxu Zheng

Affiliation

¹ Department of Geriatrics, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, China. Electronic address: [email protected].

PMID: 24140943
DOI: 10.1016/j.resp.2013.09.011

Abstract

Our objective was to investigate the pathogenesis pathways of idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) induced animal models of experimental lung fibrosis were used. CHIP assay was executed to find the link between Smad3 and IL-31, and the expressions of TGF-β1, Smad3, IL-31 and STAT1 were detected to find whether they were similar with each other. We found that in the early injury or inflammation of the animal model, BLM promoted the development of inflammation, leading to severe pulmonary fibrosis. Then the expression of TGF-β1 and Smad3 increased. Activated Smad3 bound to the IL-31 promoter region, followed by the activation of JAK-STAT pathways. The inhibitor of TGF-β1 receptor decreased the IL-31 expression and knocking-down of IL-31 also decreased the STAT1 expression. We conclude that there is a pathway of pathogenesis in BLM-induced mouse model that involves the TGF-β, IL-31 and JAKs/STATs pathway.

Keywords: Bleomycin; IL-31; Idiopathic pulmonary fibrosis; JAK-STAT; Lung; Smad3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibiotics, Antineoplastic / toxicity*
Benzamides / pharmacology
Bleomycin / toxicity*
Cells, Cultured
Dioxoles / pharmacology
Disease Models, Animal
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Fibroblasts / drug effects
Fibroblasts / metabolism
Gene Expression Regulation / drug effects*
Idiopathic Pulmonary Fibrosis / etiology*
Idiopathic Pulmonary Fibrosis / metabolism*
Interleukins / genetics
Interleukins / metabolism
Lung / cytology
Lung Injury / chemically induced*
Lung Injury / complications*
Mice
STAT1 Transcription Factor / genetics
STAT1 Transcription Factor / metabolism
Signal Transduction / drug effects*
Signal Transduction / physiology
Time Factors
Transforming Growth Factor beta1 / genetics
Transforming Growth Factor beta1 / metabolism

Substances

4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
Antibiotics, Antineoplastic
Benzamides
Dioxoles
Enzyme Inhibitors
Interleukins
STAT1 Transcription Factor
Stat1 protein, mouse
Transforming Growth Factor beta1
interleukin-31, mouse
Bleomycin