Abstract
BackgroundSeveral 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.MethodsThe 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.ResultsBLM-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.ConclusionsThese 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.
Highlights
Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis
The objective of this study is to investigate whether Tauroursodeoxycholic acid (TUDCA) has a therapeutic effect on BLM-induced EMT and subsequent lung fibrosis in a mouse model
TUDCA mitigates BLM‐induced pulmonary histological damage and collagen deposition in mice There was no death in Control and TUDCA groups
Summary
Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. This study aimed to investigate the preven‐ tive effects of TUDCA on BLM-induced EMT and lung fibrosis. Tong et al BMC Pulm Med (2021) 21:149 epithelial-mesenchymal transition (EMT) play a vital role in the pathogenesis of BLM-induced lung fibrosis [7]. Animal experiment showed that administration with antioxidant alleviated BLM-induced lung fibrosis [10]. Several studies have confirmed that endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in BLM-induced pulmonary EMT and lung fibrosis [11, 12]. Further study is required to determine whether TUDCA alleviates BLM-induced pulmonary fibrosis
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