title: Inositol-requiring protein 1 - X-box-binding protein 1 pathway promotes epithelial-mesenchymal transition via mediating snail expression in pulmonary fibrosis.
abstract: Epithelial-mesenchymal transition (EMT) is a complex biological program during which cells loss epithelial phenotype and acquire mesenchymal features. EMT is thought to be involved in the pathogenesis of various fibrotic diseases including pulmonary fibrosis (PF). Recent studies suggest that endoplasmic reticulum (ER) stress is associated with EMT in the progression of PF. However, the exact mechanism is unclear. Here, we developed a PF model with bleomycin (BLM) administration in rats and conducted several simulation experiments in alveolar epithelial cell (AECs) RLE-6TN to unravel the role of inositol-requiring protein 1 (IRE1) - X-box-binding protein 1 (XBP1) signal pathway in ER stress-induced EMT in PF. First, we observed that ER stress was occurred in type II AECs accompanied by EMT in BLM-induced PF. Then we explored the role of IRE1-XBP1-snail pathway in transforming growth factor (TGF)-β1/tunicamycin (TM)-induced EMT. When TGF-β1/TM was treated on AECs, IRE1 and XBP1 were overexpressed, meanwhile, snail expression was upregulated accompanied with EMT. However, when IRE1 or XBP1 was knockdown, TGF-β1/TM-induced EMT were blocked while the expression of snail was inhibited. Then we silenced snail and found that TGF-β1/TM-induced EMT were also suppressed, but it had no effect on the up-regulated expression of IRE1 and XBP1. Thus, we concluded that IRE1-XBP1 pathway promotes EMT via mediating snail expression in PF.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Mo
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, China; The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, China; The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Cui
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: De-Lin
authors.initials: DL
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, China; Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
authors.forename: Liu-Cheng
authors.initials: LC
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, China; The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address: gaojianayfy@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605545:Xbp1 protein, rat; C486557:Ern2 protein, rat; D017346:Protein Serine-Threonine Kinases
keywords: Endoplasmic reticulum stress; Epithelial–mesenchymal transition; Inositol-requiring protein 1 – X-box-binding protein 1 pathway; Pulmonary fibrosis; Snail