Department of Life Science, University of Seoul, Seoul 02504, Korea.
Present address: Cell Therapy Research Center, GC LabCell, Yongin 16924, Korea.
Mol Cells. 2020 Nov 30;43(11):945-952. doi: 10.14348/molcells.2020.0100.
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 and 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 and 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.
缺氧通过激活主转录因子缺氧诱导因子-1α（HIF-1α）诱导几种基因的表达。本研究表明，缺氧以 HIF-1α依赖性方式强烈诱导两种羧肽酶（CP）CPA4 和 CPE 的表达。 和 基因的缺氧诱导伴随着 HIF-1α的募集和其启动子区域中活性组蛋白修饰 H3K4me3 的上调。 在人脂肪细胞、人脂肪来源干细胞和人原代成纤维细胞中观察到 和 基因的缺氧反应，但在小鼠原代脂肪细胞祖细胞中没有观察到。CPA4 和 CPE 已被鉴定为分泌外肽酶，可降解和加工其他分泌蛋白和基质蛋白。这一发现表明，缺氧通过诱导不仅脂肪因子而且还诱导 CPA4 和 CPE 等肽酶的表达，改变肥胖缺氧脂肪组织的微环境。
