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This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/L267    most recent 90528.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Clerici, C. Articles by Planès, C. Search for Related Content PubMed PubMed Citation Articles by Clerici, C. Articles by Planès, C.

REVIEW

Gene regulation in the adaptive process to hypoxia in lung epithelial cells

¹Université Denis Diderot-Paris 7; ²AP-HP, Hôpital Bichat-Claude Bernard, Service de Physiologie, Paris; ³Institut National de la Santé et de la Recherche Médicale, U 773, CRB3, Paris; ⁴Université Paris 13; ⁵AP-HP, Hôpital Avicenne, Service de Physiologie, Bobigny; and ⁶EA2363, UFR Santé, Médecine et Biologie Humaine, Bobigny, France

ABSTRACT

Lung alveolar epithelial cells are normally very well oxygenated but may be exposed to hypoxia in many pathological conditions such as pulmonary edema, acute respiratory distress syndrome, chronic obstructive pulmonary diseases, or in some environmental conditions such ascent to high altitude. The ability of alveolar epithelial cells to cope with low oxygen tensions is crucial to maintain the structural and functional integrity of the alveolar epithelium. Alveolar epithelial cells appear to be remarkably tolerant to oxygen deprivation as they are able to maintain adequate cellular ATP content during prolonged hypoxic exposure when mitochondrial oxidative phosphorylation is limited. This property mostly relies on the ability of the cells to rapidly modify their gene expression program, stimulating the expression of genes involved in anaerobic energy supply and repressing expression of genes involved in some ATP-consuming cellular processes. This adaptive strategy of the cells is mostly, but not entirely, dependent on the expression of hypoxia-inducible factors (HIFs), known to be responsible for orchestrating a large number of hypoxia-sensitive genes. This review focuses on the role of HIF isoforms expressed in alveolar epithelial cells exposed to hypoxia and on the specific hypoxic gene regulation that takes place in alveolar epithelial cells either through HIF-dependent or -independent pathways.

hypoxia-inducible factors; glucose transport; glycolytic enzymes; apoptosis; proliferation; vascular endothelial growth factor; sodium transporters