Hypoxia-induced compensatory effect as related to Shh and HIF-1alpha in ischemia embryo rat heart.
Mol Cell Biochem. 2008 Apr;311(1-2):179-87
Authors: Hwang JM, Weng YJ, Lin JA, Bau DT, Ko FY, Tsai FJ, Tsai CH, Wu CH, Lin PC, Huang CY, Kuo WW
Chronic cardiac ischemia/hypoxia induces coronary collateral formation and cardiomyocyte proliferation. Hypoxia can induce cellular adaptive responses, such as synthesis of VEGF for angiogenesis and IGF-2 for proliferation. Both reduce apoptotic effects to minimize injury or damage. To investigate the mechanism of neoangiogenesis and proliferation of fetal heart under umbilical cord compression situation, we used H9c2 cardiomyoblast cell culture, and in vivo embryonic hearts as our study models. Results showed hypoxia induced not only the increase of IGF-2 and VEGF expression but also the activation of their upstream regulatory genes, HIF-1alpha and Shh. The relationship between HIF-1alpha and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh and HIF-1alpha signaling, respectively, in the cardiomyoblast cell culture under hypoxia. We found that the two inhibitors not only blocked their own signal pathway, but also inhibited each other. The observations revealed when fetal heart under hypoxia that HIF-1alpha and Shh pathways maybe involve in cell proliferation and neoangiogenesis to minimize injury or damage, whereas the complex cross-talk between the two pathways remains unknown.
PMID: 18228117 [PubMed - indexed for MEDLINE]
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PubMed: hedgehog
NCBI: db=PubMed; Term=hedgehog
