Hypoxia-inducible factor-1α regulates CD55 in airway epithelium

Pankita H. Pandya, Amanda J. Fisher, Elizabeth A. Mickler, Constance J. Temm, Kelsey P. Lipking, Adam Gracon, Katia Rothhaar, George E. Sandusky, Mary Murray, Karen Pollok, Jamie Renbarger, Janice S. Blum, Tim Lahm, David S. Wilkes

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Airway epithelial CD55 down-regulation occurs in several hypoxiaassociated pulmonary diseases, but the mechanism is unknown. Using in vivo and in vitro assays of pharmacologic inhibition and gene silencing, the current study investigated the role of hypoxiainducible factor (HIF)-1α in regulating airway epithelial CD55 expression. Hypoxia down-regulated CD55 expression on smallairway epithelial cells in vitro, and in murine lungs in vivo; the latter was associated with local complement activation. Treatment with pharmacologic inhibition or silencing of HIF-1α during hypoxiarecovered CD55 expression in small-airway epithelial cells.HIF-1α overexpression or blockade, in vitro or in vivo, down-regulated CD55 expression. Collectively, these data show a key role for HIF-1α in regulating the expression of CD55 on airway epithelium.

Original languageEnglish (US)
Pages (from-to)889-898
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume55
Issue number6
DOIs
StatePublished - Dec 2016

Keywords

  • Complement regulatory proteins
  • Hypoxia
  • Lung

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Pandya, P. H., Fisher, A. J., Mickler, E. A., Temm, C. J., Lipking, K. P., Gracon, A., Rothhaar, K., Sandusky, G. E., Murray, M., Pollok, K., Renbarger, J., Blum, J. S., Lahm, T., & Wilkes, D. S. (2016). Hypoxia-inducible factor-1α regulates CD55 in airway epithelium. American journal of respiratory cell and molecular biology, 55(6), 889-898. https://doi.org/10.1165/rcmb.2015-0237OC