Glycochenodeoxycholate induces rat alveolar epithelial type II cell death and inhibits surfactant secretion in vitro

Zhangxue, Hu; Гао, Мін; Zhao, Jingping; Shi, Yuan; li, Wang; Huapei, Song; Li, Rui; Zhang, Chunyu

doi:10.1016/j.freeradbiomed.2012.04.027

Cited by 16 publications

(15 citation statements)

References 23 publications

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“…Additionally, Gao et al reported that the activation of autophagy protected against cholestasis‐induced liver injury in a bile duct ligation model . Previous studies have suggested that the intracellular accumulation of hydrophobic bile acids contribute to cholestasis‐associated liver injury . In this study, rats that received rapamycin had lower serum concentrations of ALT, AST, TB, and DB (Figure ).…”

Section: Discussionsupporting

confidence: 50%

Autophagy May Protect Against Parenteral Nutrition‐Associated Liver Disease by Suppressing Endoplasmic Reticulum Stress

Zhang

Yan²,

Wang

et al. 2018

J Parenter Enteral Nutr

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Section: Discussionsupporting

confidence: 50%

Autophagy May Protect Against Parenteral Nutrition‐Associated Liver Disease by Suppressing Endoplasmic Reticulum Stress

Zhang

Yan²,

Wang

et al. 2018

J Parenter Enteral Nutr

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“…The aberrant injured or activated AECs undergoing EMT serve as one source of myofibroblasts in IPF lungs . We found that LCA, DCA and CDCA reduced cell viability and enhanced reactive oxygen species production, which is consistent with previous findings . LCA was more toxic than DCA and CDCA, which may be due to its highest hydrophobicity .…”

Section: Discussionsupporting

confidence: 91%

“…Recent data suggest that elevated levels of bile acids and pepsin in bronchoalveolar lavage fluid (BALF) and sputum are effective biomarkers for diagnosis and treatment of gastropulmonary aspiration . Bile acid aspiration has been implicated in lung injury and airway fibrosis . The presence/concentration of bile acids in BALF has been correlated with the degree of lung fibrosis in patients with IPF, suggesting bile acid microaspiration may be an active player in the development and/or progression of IPF.…”

Section: Introductionmentioning

confidence: 99%

Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor‐dependent and independent pathways

Cai

Xue

et al. 2016

Respirology

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Background and objective:The roles of bile acid microaspiration and bile acid-activated farnesoid X receptor (FXR) in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear. We hypothesized that bile acids activate alveolar epithelial cells (AECs) and lung fibroblasts, which may be regulated by FXR activation. Methods: Human AECs and normal or IPF-derived lung fibroblast cells were incubated with the three major bile acids: lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The AECs injury indices, epithelial-mesenchymal transition (EMT) and lung fibroblast activation were evaluated. FXR expression in IPF lungs and the roles of FXR and FXR-independent pathways in bile acid-induced profibrotic effects were also investigated. Results: LCA, DCA and CDCA reduced cell viability and increased intracellular reactive oxygen species (ROS) production in A549 cells. They all induced EMT, as shown by enhanced α-SMA and vimentin and decreased E-cadherin levels. LCA directly induced differentiation of lung fibroblasts to myofibroblasts. All three bile acids promoted cellular migration but not proliferation of lung fibroblasts. FXR expression was upregulated in IPF lungs, and inhibition of FXR restrained the bile acid-induced EMT and lung fibroblast activation. Differentiation and proliferation were enhanced in lung fibroblasts exposed to conditioned medium from bile acid-stimulated A549 cells, which contained increased levels of profibrotic factors. TGF-β/Smad3 signaling was also involved in the bile acid-induced EMT and lung fibroblast differentiation. Conclusion: Bile acid microaspiration may promote the development of pulmonary fibrosis by inducing activation of AECs and lung fibroblasts via FXR-dependent and independent pathways.

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“…Bile acids contribute to the development of liver injury by causing hepatocyte and biliary epithelial cell inflammatory responses and/or apoptosis [25]–[29]. Both bile acids and TNF-α have also been shown to reduce surfactant protein production and enhance apoptosis in AT2 cells [30]–[33].…”

Section: Introductionmentioning

confidence: 99%

Alveolar Type II Epithelial Cell Dysfunction in Rat Experimental Hepatopulmonary Syndrome (HPS)

Batra

et al. 2014

PLoS ONE

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The hepatopulmonary syndrome (HPS) develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2) play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D) which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL). We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064) induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.

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Glycochenodeoxycholate induces rat alveolar epithelial type II cell death and inhibits surfactant secretion in vitro

Cited by 16 publications

References 23 publications

Autophagy May Protect Against Parenteral Nutrition‐Associated Liver Disease by Suppressing Endoplasmic Reticulum Stress

Autophagy May Protect Against Parenteral Nutrition‐Associated Liver Disease by Suppressing Endoplasmic Reticulum Stress

Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor‐dependent and independent pathways

Alveolar Type II Epithelial Cell Dysfunction in Rat Experimental Hepatopulmonary Syndrome (HPS)

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