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KMID : 0578320200430110945
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Molecules and Cells
2020 Volume.43 No. 11 p.945 ~ p.952
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HIF-1α-Dependent Induction of Carboxypeptidase A4 and Carboxypeptidase E in Hypoxic Human Adipose-Derived Stem Cells
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Moon Yun-Won
Moon Ram-Hee
Roh Hyun-Soo
Chang Soo-Jeong
Lee Seong-Yeol
Park Hyun-Sung
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Abstract
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Hypoxia induces the expression of several genes through the activation of a master transcription factor, hypoxia-inducible factor (HIF)-1α. This study shows that hypoxia strongly induced the expression of two carboxypeptidases (CP), CPA4 and CPE, in an HIF-1α-dependent manner. The hypoxic induction of CPA4 and CPE gene was accompanied by the recruitment of HIF-1α and upregulation in the active histone modification, H3K4me3, at their promoter regions. The hypoxic responsiveness of CPA4 and CPE genes was observed in human adipocytes, human adipose-derived stem cells, and human primary fibroblasts but not mouse primary adipocyte progenitor cells. CPA4 and CPE have been identified as secreted exopeptidases that degrade and process other secreted proteins and matrix proteins. This finding suggests that hypoxia changes the microenvironment of the obese hypoxic adipose tissue by inducing the expression of not only adipokines but also peptidases such as CPA4 and CPE.
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KEYWORD
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carboxypeptidase A4, carboxypeptidase E, human adipose-derived stem cells, hypoxia, hypoxia-inducible factor-1α
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