Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart (original) (raw)

Abstract

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-1α and Shh. The relationship between HIF-1α and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh and HIF-1α 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-1α 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.

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Acknowledgments

This work was supported by grant from the National Science Council of Republic of China (NSC94-2316-B-039-002).

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Authors and Affiliations

  1. School of Applied Chemistry, Chung-Shan Medical University, Taichung, Taiwan
    Jin-Ming Hwang
  2. Department of Veterinary Medicine, National Chung-Hsing University, Taichung, 402, Taiwan
    Yi-Jiun Weng
  3. Graduate Institute of Basic Medical Science, China Medical University, Taichung, 404, Taiwan
    James A. Lin & Chih-Yang Huang
  4. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, 404, Taiwan
    Da-Tian Bau, Fu-Yang Ko, Fuu-Jen Tsai & Chih-Yang Huang
  5. Department of Pediatrics, Medical Research and Medical Genetics, China Medical College Hospital, Taichung, Taiwan
    Fuu-Jen Tsai
  6. Department of Healthcare Administration, Asia University, Taichung, Taiwan
    Chang-Hai Tsai
  7. Department of Biological Science and Technology, School of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 404, Taiwan
    Chieh-Hsi Wu & Wei-Wen Kuo
  8. School of Medical Laboratory and Biotechnology, Chung-Shan Medical University, Taichung, 402, Taiwan
    Pei-Cheng Lin
  9. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
    Chih-Yang Huang

Authors

  1. Jin-Ming Hwang
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  2. Yi-Jiun Weng
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  3. James A. Lin
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  4. Da-Tian Bau
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  5. Fu-Yang Ko
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  6. Fuu-Jen Tsai
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  7. Chang-Hai Tsai
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  8. Chieh-Hsi Wu
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  9. Pei-Cheng Lin
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  10. Chih-Yang Huang
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  11. Wei-Wen Kuo
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Corresponding author

Correspondence toWei-Wen Kuo.

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Pei-Cheng Lin, Chih-Yang Huang, and Wei-Wen Kuo contributed equally to this work.

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Hwang, JM., Weng, YJ., Lin, J.A. et al. Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart.Mol Cell Biochem 311, 179–187 (2008). https://doi.org/10.1007/s11010-008-9708-6

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