Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 293, Issue 4, Pages L913-L922Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00459.2006
Keywords
cobalt; fetal bovine serum
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Airway smooth muscle (ASM) cells are characterized by phenotypic plasticity and can switch between differentiated and proliferative phenotypes. In rabbit tracheal ASM cells that had been differentiated in vitro by serum starvation, readdition of FBS caused initiation of proliferation and induction of nuclear and transcriptionally active hypoxia-inducible factor ( HIF)-1 alpha. In addition, FBS stimulated the induction of HIF-1 alpha by the hypoxia mimetic cobalt. Treatment with actinomycin D, cycloheximide, the phosphatidylinositol 3-kinase inhibitors LY-294002 and wortmannin or the reactive oxygen species scavenger diphenyleneiodonium inhibited the FBS-dependent induction of HIF-1 alpha. These data indicate that, in differentiated ASM cells, FBS upregulates HIF-1 alpha by a transcription-, translation-, phosphatidylinositol 3-kinase, and reactive oxygen species-dependent mechanism. Interestingly, addition of FBS and cobalt also induced HIF-1 alpha in organ cultures of rabbit trachea strips and synergistically increased their contractile response to ACh, suggesting that HIF-1 alpha might be implicated in airway hypercontractility.
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