1 State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University , Nanjing, China .
2 Center of Clinical Reproductive Medicine, Affiliated Changzhou Women's and Children's Healthcare Hospital of Nanjing Medical University , Changzhou, China .
Stem Cells Dev. 2018 Aug 1;27(15):1021-1032. doi: 10.1089/scd.2017.0287. Epub 2018 Jun 29.
Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in the regulation of the renin-angiotensin system. In this study, we used reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis to confirm that somatic ACE (sACE), but not testicular ACE (tACE), is expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. sACE was found to play an important role in SSC self-renewal through the regulation of MAPK-dependent cell proliferation.
精原干细胞（SSC）自我更新是精子发生所必需的。血管紧张素转换酶（ACE）是一种锌二肽羧基肽酶，在肾素-血管紧张素系统的调节中起着关键作用。在这项研究中，我们使用逆转录-聚合酶链反应（RT-PCR）和 Western blot 分析证实，体细胞 ACE（sACE），而不是睾丸 ACE（tACE），在产后第 7 天之前和在培养的 SSCs 中表达于小鼠睾丸。我们的结果表明 sACE 位于 SSCs 的膜上。用 ACE 竞争性抑制剂卡托普利处理培养的 SSCs 被发现抑制 sACE 活性，并显著降低 SSCs 的增殖率。微阵列分析鉴定出 651 个具有显著差异表达的基因。京都基因与基因组百科全书（KEGG）通路分析表明，这些差异表达的基因主要参与丝裂原激活蛋白激酶（MAPK）信号通路。sACE 通过调节 MAPK 依赖性细胞增殖，在 SSC 自我更新中发挥重要作用。
