Hypoxia-Inducible Factor-1α Regulates CD55 in Airway Epithelium

• Published in: American journal of respiratory cell and molecular biology Vol. 55; no. 6; pp. 889 - 898
• Main Authors: Pandya, Pankita H, Fisher, Amanda J, Mickler, Elizabeth A, Temm, Constance J, Lipking, Kelsey P, Gracon, Adam, Rothhaar, Katia, Sandusky, George E, Murray, Mary, Pollok, Karen, Renbarger, Jamie, Blum, Janice S, Lahm, Tim, Wilkes, David S
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01-12-2016
• Subjects: Amino Acids, Dicarboxylic - pharmacology; Animals; CD55 Antigens - metabolism; Cell Hypoxia - drug effects; Complement Activation - drug effects; Down-Regulation - drug effects; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelium - drug effects; Epithelium - metabolism; Gene Silencing - drug effects; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Lung - metabolism; Male; Mice, Inbred C57BL; Original Research; lung; hypoxia; complement regulatory proteins
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2015-0237OC

Airway epithelial CD55 down-regulation occurs in several hypoxia-associated 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 hypoxia-inducible factor (HIF)-1α in regulating airway epithelial CD55 expression. Hypoxia down-regulated CD55 expression on small-airway 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 hypoxia-recovered 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.