School of Biomedical Sciences & Pharmacy, Mothers & Babies Research Centre, University of Newcastle, Hunter Medical Research Institute & John Hunter Hospital, Newcastle, NSW 2300, Australia.
Placenta. 2012 Aug;33(8):634-9. doi: 10.1016/j.placenta.2012.05.001. Epub 2012 May 28.
The renin-angiotensin system (RAS) is implicated in placentation. We determined which RAS pathways are present in two trophoblast cell lines (HTR-8/SVneo and BeWo cells) and the effects of cAMP, which stimulates renal renin.
The effect of cAMP on RAS gene expression and on prorenin and angiotensin peptides in HTR-8/SVneo and BeWo cells were investigated.
In HTR-8/SVneo cells, prorenin mRNA (REN) and protein, (pro)renin receptor (ATP6AP2) and angiotensin II type 1 receptor (AGTR1) were stimulated by cAMP (P < 0.05, P < 0.05, P < 0.001 and P < 0.05, respectively). HTR-8/SVneo cells also expressed angiotensinogen (AGT) and angiotensin converting enzyme 1 (ACE1), but did not express AGTR2 or ACE2 nor the Ang 1-7 receptor (MAS1). BeWo cells did not express REN, and REN was not inducible by cAMP, but cAMP increased ACE2 and MAS1 (both P < 0.05) and decreased AGT (P < 0.05). BeWo cells expressed AGT, ACE1, ACE2 and MAS1 but not ATP6AP2, AGTR1 nor AGTR2. There was net destruction of Ang II in media from HTR-8/SVneo and BeWo incubations and net production of Ang 1-7 by BeWo and untreated HTR-8/SVneo cells.
HTR-8/SVneo cells express REN and produce prorenin as well as expressing other RAS genes likely to regulate Ang II/AT(1)R interactions and respond to cAMP, like renal renin-secreting cells. They are more similar to early gestation placentae and are therefore useful for studying effects of renin/ACE/Ang II/AT₁R on cell function. BeWo cells express the ACE2/Ang 1-7/Mas pathway, which is sensitive to cAMP and therefore are useful for studying the effects of ACE2/Ang 1-7/Mas on trophoblast function.
肾素-血管紧张素系统（RAS）参与胎盘形成。我们确定了两种滋养层细胞系（HTR-8/SVneo 和 BeWo 细胞）中存在哪些 RAS 途径，以及刺激肾素的 cAMP 的作用。
研究了 cAMP 对 HTR-8/SVneo 和 BeWo 细胞中 RAS 基因表达以及前肾素和血管紧张素肽的影响。
在 HTR-8/SVneo 细胞中，cAMP 刺激前肾素 mRNA（REN）和蛋白（pro）肾素受体（ATP6AP2）和血管紧张素 II 型 1 受体（AGTR1）的表达（P < 0.05、P < 0.05、P < 0.001 和 P < 0.05，分别）。HTR-8/SVneo 细胞还表达血管紧张素原（AGT）和血管紧张素转换酶 1（ACE1），但不表达 AGTR2 或 ACE2 以及 Ang 1-7 受体（MAS1）。BeWo 细胞不表达 REN，cAMP 也不能诱导 REN，但 cAMP 增加了 ACE2 和 MAS1（均 P < 0.05）并降低了 AGT（P < 0.05）。BeWo 细胞表达 AGT、ACE1、ACE2 和 MAS1，但不表达 ATP6AP2、AGTR1 或 AGTR2。HTR-8/SVneo 和 BeWo 孵育物中的介质中存在 Ang II 的净破坏，而未经处理的 HTR-8/SVneo 细胞中存在 Ang 1-7 的净产生。
HTR-8/SVneo 细胞表达 REN 并产生前肾素，以及表达其他可能调节 Ang II/AT(1)R 相互作用并对 cAMP 作出反应的 RAS 基因，就像分泌肾素的细胞一样。它们与早期妊娠胎盘更相似，因此可用于研究肾素/ACE/Ang II/AT₁R 对细胞功能的影响。BeWo 细胞表达 ACE2/Ang 1-7/Mas 途径，该途径对 cAMP 敏感，因此可用于研究 ACE2/Ang 1-7/Mas 对滋养层细胞功能的影响。
