Morphologic Damage of Rat Alveolar Epithelial Type II Cells Induced by Bile Acids Could Be Ameliorated by Farnesoid X Receptor Inhibitor Z-Guggulsterone In Vitro

Wang, Jie‐Qin; Huang, Yihong; Hou, Xusheng; Wu, Wei; Nie, Lei; Tian, Yuan; Lu, Yao; Yin, Yanru

doi:10.1155/2016/9283204

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…Furthermore, the presence of bile in the airways can lead to biofilm formation by cystic fibrosis-associated respiratory pathogens, which may be an important factor contributing to airway colonization by opportunistic microorganisms (458). The molecular pathways by which bile acids exert their actions in the airways are still poorly defined, although recent studies have implicated FXR in mediating their effects on airway epithelial survival, epithelial-mesenchymal transition, and activation of fibroblasts (59,485). However, other studies demonstrating protective actions of FXR against airway inflammation and fibrosis suggest that there is still much to be learned of how this, and indeed other bile acid receptors, contribute to airway health and disease (78).…”

Section: F Bile Acids and The Airwaysmentioning

confidence: 99%

Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease

Hegyi

Maléth

Walters

et al. 2018

Physiological Reviews

210

152

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Epithelial cells line the entire surface of the gastrointestinal tract and its accessory organs where they primarily function in transporting digestive enzymes, nutrients, electrolytes, and fluid to and from the luminal contents. At the same time, epithelial cells are responsible for forming a physical and biochemical barrier that prevents the entry into the body of harmful agents, such as bacteria and their toxins. Dysregulation of epithelial transport and barrier function is associated with the pathogenesis of a number of conditions throughout the intestine, such as inflammatory bowel disease, chronic diarrhea, pancreatitis, reflux esophagitis, and cancer. Driven by discovery of specific receptors on intestinal epithelial cells, new insights into mechanisms that control their synthesis and enterohepatic circulation, and a growing appreciation of their roles as bioactive bacterial metabolites, bile acids are currently receiving a great deal of interest as critical regulators of epithelial function in health and disease. This review aims to summarize recent advances in this field and to highlight how bile acids are now emerging as exciting new targets for disease intervention.

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Section: F Bile Acids and The Airwaysmentioning

confidence: 99%

Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease

Hegyi

Maléth

Walters

et al. 2018

Physiological Reviews

210

152

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“…Subsequently, the cells were embedded and cut into ultrathin sections (~60 nm in thickness). The sections were stained with uranyl acetate in the dark for 20 min and washed three times with double-distilled water [ 23 ]. After the sections were dried with filter paper, they were observed by using a Hitachi HT7700 transmission electron microscope.…”

Section: Methodsmentioning

confidence: 99%

Hyperoxia induces alveolar epithelial cell apoptosis by regulating mitochondrial function through small mothers against decapentaplegic 3 (SMAD3) and extracellular signal-regulated kinase 1/2 (ERK1/2)

Jiang

Wang

et al. 2021

Bioengineered

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Oxygen therapy and mechanical ventilation are widely used to treat and manage neonatal emergencies in critically ill newborns. However, they are often associated with adverse effects and result in conditions such as chronic lung disease and bronchopulmonary dysplasia. Hence, aclear understanding of the mechanisms underlying hyperoxia-induced lung damage is crucial in order to mitigate the side effects of oxygen-based therapy. Here, we have established an in vitro model of hyperoxia-induced lung damage in type II alveolar epithelial cells (AECIIs) and delineated the molecular basis of oxygen therapy-induced impaired alveolar development. Thus, AECIIs were exposed to a hyperoxic environment and their cell viability, cell cycle progression, apoptosis, mitochondrial integrity and dynamics, and energy metabolism were assessed. The results showed that hyperoxia has no significant effect as an inhibitor of SMAD3 and ERK1/2 in AECIIs, but leads to significant inhibition of cell viability. Further, hyperoxia was found to promote AECII apoptosis and mitochondrial, whereas chemical inhibition of SMAD3 or ERK1/2 further exacerbated the detrimental effects of hyperoxia in AECIIs. Overall, these findings presented herein demonstrate the critical role of SMAD/ERK signaling in the regulation of AECII behavior in varying oxygen environments. Thus, this study offers novel insights for the prevention of neonatal lung dysfunction in premature infants.

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“…FXR is not only located in alveolar epithelial type I cells (AECIs) but also in alveolar epithelial type II cells (ATECIIs) [ 69 ]. ATII cells are multifunctional cells that synthesize and secrete lung surfactants and can participate in the immune response by producing AECIs [ 70 ].…”

Section: Fxr and Respiratory Diseasesmentioning

confidence: 99%

“…Several studies have observed that FXR exists not only in pulmonary vascular endothelial cells but also in epithelial cells [ 69 , 78 ]. FXR plays an important role in maintaining lung function by inhibiting lung inflammatory response, producing lung surfactants, and promoting alveolar repair to resist lung injury.…”

Section: Fxr and Respiratory Diseasesmentioning

confidence: 99%

Role of Farnesoid X Receptor in the Pathogenesis of Respiratory Diseases

Chen

2020

Canadian Respiratory Journal

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Farnesoid X receptor (FXR) is a bile acid receptor encoded by the Nr1h4 gene. FXR plays an important role in maintaining the stability of the internal environment and the integrity of many organs, including the liver and intestines. The expression of FXR in nondigestible tissues other than in the liver and small intestine is known as the expression of “nonclassical” bile acid target organs, such as blood vessels and lungs. In recent years, several studies have shown that FXR is widely involved in the pathogenesis of various respiratory diseases, such as chronic obstructive pulmonary disease, bronchial asthma, and idiopathic pulmonary fibrosis. Moreover, a number of works have confirmed that FXR can regulate the bile acid metabolism in the body and exert its anti-inflammatory and antifibrotic effects in the airways and lungs. In addition, FXR may be used as a potential therapeutic target for some respiratory diseases. For example, FXR can regulate the tumor microenvironment by regulating the balance of inflammatory and immune responses in the body to promote the occurrence and development of non-small-cell lung cancer (NSCLC), thereby being considered a potential target for immunotherapy of NSCLC. In this article, we provide an overview of the internal relationship between FXR and respiratory diseases to track the progress that has been achieved thus far in this direction and suggest potential therapeutic prospects of FXR in respiratory diseases.

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Morphologic Damage of Rat Alveolar Epithelial Type II Cells Induced by Bile Acids Could Be Ameliorated by Farnesoid X Receptor Inhibitor Z-Guggulsterone In Vitro

Cited by 6 publications

References 21 publications

Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease

Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease

Hyperoxia induces alveolar epithelial cell apoptosis by regulating mitochondrial function through small mothers against decapentaplegic 3 (SMAD3) and extracellular signal-regulated kinase 1/2 (ERK1/2)

Role of Farnesoid X Receptor in the Pathogenesis of Respiratory Diseases

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