Chronic microaspiration of bile acids induces lung fibrosis through multiple mechanisms in rats

In this study, a rat model of bile acid microaspiration was established by weekly intratracheal instillation of three major bile acids including chenodeoxycholic acid (CDCA), deoxycholic acid (DCA) and lithocholic acid (LCA) . Repeated microaspiration of CDCA, DCA and LCA caused fibrotic changes, including alveolar wall thickening and extensive collagen deposition, in rat lungs. Bile acid microaspiration also induced alveolar epithelial-mesenchymal transition (EMT), as indicated by upregulation of  mesenchymal markers α-smooth muscle actin (α-SMA) and vimentin, as well as downregulaton of epithelial markers E-cadherin and cytokeratin in alveolar epithelium of rat lungs. The expression of fibrogenic mediators, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and periostin, was significantly elevated in rat lungs exposed to microaspiration of bile acids. Furthermore, microaspiration of bile acids also induced phospho-Smad3 and farnesoid X receptor (FXR) expression in rat lungs. Our findings suggest that microaspiration of bile acids could promote the development of pulmonary fibrosis in vivo , possibly via stimulating fibrogenic mediators expression and activating TGF-β1/Smad3 signaling and FXR.

Source: Clinical Science - March 24, 2017 Category: Biomedical Science Authors: chen, B., You, W. J., Liu, X. Q., Xue, S., Qin, H., Jiang, H. D. Tags: PublishAheadOfPrint Source Type: research