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Am J Physiol Lung Cell Mol Physiol 293: L913-L922, 2007. First published July 27, 2007; doi:10.1152/ajplung.00459.2006
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Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1{alpha} and airway responsiveness to ACh

Georgia Chachami,1,2 Apostolia Hatziefthimiou,1 Panagiotis Liakos,2 Maria G. Ioannou,3 Georgios K. Koukoulis,3 Sofia Bonanou,2 Paschalis-Adam Molyvdas,1 George Simos,2 and Efrosyni Paraskeva1

Departments of 1Physiology, 2Biochemistry, and 3Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Thessaly, Greece

Submitted 20 November 2006 ; accepted in final form 16 July 2007

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.

cobalt; fetal bovine serum



Address for reprint requests and other correspondence: E. Paraskeva or G. Simos, Papakiriazi 22, 41222 Larissa, Greece (e-mail: fparaskeva{at}med.uth.gr or simos{at}med.uth.gr)







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