Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS)

Wenli Yang, Bingqian Hu, Wei Wu, Sachin Batra, Michael R. Blackburn, Joseph L. Alcorn, Michael B. Fallon, Junlan Zhang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere113451
JournalPloS one
Volume9
Issue number11
DOIs
StatePublished - Nov 24 2014
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yang, W., Hu, B., Wu, W., Batra, S., Blackburn, M. R., Alcorn, J. L., Fallon, M. B., & Zhang, J. (2014). Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS). PloS one, 9(11), [e113451]. https://doi.org/10.1371/journal.pone.0113451