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- Title
Tauroursodeoxycholic acid alleviates pulmonary endoplasmic reticulum stress and epithelial-mesenchymal transition in bleomycin-induced lung fibrosis.
- Authors
Tong, Bin; Fu, Lin; Hu, Biao; Zhang, Zhi-Cheng; Tan, Zhu-Xia; Li, Se-Ruo; Chen, Yuan-Hua; Zhang, Cheng; Wang, Hua; Xu, De-Xiang; Zhao, Hui
- Abstract
<bold>Background: </bold>Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis.<bold>Methods: </bold>The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily.<bold>Results: </bold>BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA.<bold>Conclusions: </bold>These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.
- Subjects
PULMONARY fibrosis; EPITHELIAL-mesenchymal transition; ENDOPLASMIC reticulum; IDIOPATHIC pulmonary fibrosis; OXIDATIVE stress
- Publication
BMC Pulmonary Medicine, 2021, Vol 21, Issue 1, p1
- ISSN
1471-2466
- Publication type
journal article
- DOI
10.1186/s12890-021-01514-6