Roperto Sante, Russo Valeria, Urraro Chiara, Restucci Brunella, Corrado Federica, De Falco Francesca, Roperto Franco
Dipartimento di Medicina Veterinaria e delle Produzioni Animali, Università di Napoli Federico II, Napoli, Italy.
Dipartimento di Medicina Veterinaria e delle Produzioni Animali, Università di Napoli Federico II, Napoli, Italy.
Theriogenology. 2017 Nov;103:162-168. doi: 10.1016/j.theriogenology.2017.07.047. Epub 2017 Aug 1.
ERas is a new gene recently found in mouse embryonic stem (ES) cells and localized on the X chromosome. It plays a role in mouse ES cell survival and is constitutively active without any mutations. It was also found to be responsible for the maintenance of quiescence of the hepatic stellate cells (HSCs), liver-resident mesenchymal stem cells, the activation of which results in liver fibrosis. This gene was not present in human ES cells. ERas was found to be activated in a significant population of human gastric cancer, where ERAS may play a crucial role in gastric cancer cell survival and metastases to liver via down-regulation of E-cadherin. ERas gene has been found to be expressed both in ES cells and adult tissues of cynomolgus monkey. Cynomolgus ERAS did not promote cell proliferation or induce tumor formation. ERAS was also detected in normal and neoplastic urothelium of the urinary bladder in cattle, where bovine ERAS formed a constitutive complex with platelet derived growth factor β receptor (PDGFβR) resulting in the activation of AKT signaling. Here, molecular and morphological findings of ERAS in the full term placenta of pregnant cows have been investigated for the first time. ERAS was studied by reverse transcriptase PCR (RT-PCR). Alignment of the sequence detects a 100% identity with all transcript variant bovine ERas mRNAs, present in the GenBank database (http://www.ncbi.nlm.nih.gov). Furthermore, ERAS was detected by Western blot and investigated by real time PCR that revealed an amount of ERAS more than ERAS found in normal bovine urothelium but less than ERAS present in the liver. Immunohistochemical examination revealed the presence of ERAS protein both at the level of plasma membrane and in cytoplasm of epithelial cells lining caruncular crypts and in trophoblasts of villi. An evident ERAS immunoreactivity was also seen throughout the chorionic and uterine gland epithelium. Although this is not a functional study and further investigations will be warranted, it is conceivable that ERAS may have pleiotropic effects in the placenta, some of which, like normal urothelial cells, might lead to activation of AKT pathway. We speculate that ERAS may play a key role in cellular processes such as cell differentiation and movement. Accordingly, we believe it may be an important factor involved in trophoblast invasiveness via AKT signaling pathway. Therefore, ERas gene is a functional gene which contributes to homeostasis of bovine placenta.
ERas是最近在小鼠胚胎干细胞(ES细胞)中发现的一个新基因,定位于X染色体上。它在小鼠ES细胞存活中发挥作用,且无任何突变即组成性激活。还发现它负责维持肝星状细胞(HSCs)的静止状态,肝星状细胞是驻留在肝脏的间充质干细胞,其激活会导致肝纤维化。该基因在人类ES细胞中不存在。发现ERas在大量人类胃癌中被激活,其中ERAS可能通过下调E-钙黏蛋白在胃癌细胞存活和肝转移中起关键作用。已发现ERas基因在食蟹猴的ES细胞和成年组织中均有表达。食蟹猴的ERAS不促进细胞增殖或诱导肿瘤形成。在牛膀胱的正常和肿瘤性尿路上皮中也检测到了ERAS,其中牛的ERAS与血小板衍生生长因子β受体(PDGFβR)形成组成性复合物,导致AKT信号通路激活。在此,首次对怀孕母牛足月胎盘中ERAS的分子和形态学发现进行了研究。通过逆转录聚合酶链反应(RT-PCR)研究ERAS。序列比对检测到与GenBank数据库(http://www.ncbi.nlm.nih.gov)中存在的所有转录变体牛ERas mRNA有100%的同一性。此外,通过蛋白质免疫印迹法检测到ERAS,并通过实时PCR进行研究,结果显示ERAS的量比正常牛尿路上皮中的多,但比肝脏中的少。免疫组织化学检查显示,在肉阜隐窝内衬上皮细胞的质膜水平和细胞质中以及绒毛的滋养层中均存在ERAS蛋白。在整个绒毛膜和子宫腺上皮中也可见明显的ERAS免疫反应性。虽然这不是一项功能研究,还需要进一步研究,但可以想象ERAS可能在胎盘中具有多效性作用,其中一些作用,如在正常尿路上皮细胞中一样,可能导致AKT途径激活。我们推测ERAS可能在细胞分化和运动等细胞过程中起关键作用。因此,我们认为它可能是通过AKT信号通路参与滋养层侵袭的一个重要因素。所以,ERas基因是一个有助于维持牛胎盘内环境稳定的功能基因。