Department of Comparative Endocrinology, Medical University of Lodz, Lodz, 90-752, Poland.
Department of Comparative Endocrinology, Medical University of Lodz, Lodz, 90-752, Poland.
Biochem Biophys Res Commun. 2018 Jul 7;502(1):152-159. doi: 10.1016/j.bbrc.2018.05.138. Epub 2018 May 26.
The ACE2/Ang1-7/MAS axis was involved in the cell proliferation, migration and apoptosis of many types of reproductive tissues. The research was conducted on prostate epithelial cells, immortalized by Simian Virus 40. We examined the influence of Ang 1-7 on biological properties of PNT1A cells after 24- or 48-h treatment. The employed selective antagonists of angiotensin receptors allowed evaluation of the receptor mediating Ang1-7 action. Our data clearly indicate that Ang1-7 can decrease cell proliferation and epithelial-to-mesenchymal transition of PNT1A cells via inactivation of PI3K axis and modulation of expression of the NF-kB gene family. Furthermore, it counteracts oxidant stress and inflammation in prostate cells by inhibition of VEGF expression and MMPs activation as well as by modulating the level of ERα and ERβ. On the other hand, this heptapeptide can promote cell survival by alteration of expression of anti- and pro-apoptotic members as well as compensatory up-regulation of AR expression. Summary, the results confirm the existence of a complicated dependence networks between the various elements of the local RAS and steroid hormone receptor pathways in prostate gland. Furthermore, shows the chances of using ACE2/Ang1-7/MAS pathway as a novel therapeutic target in prevention and treatment of prostate diseases.
ACE2/Ang1-7/MAS 轴参与多种生殖组织细胞的增殖、迁移和凋亡。这项研究是在受猴病毒 40 感染的前列腺上皮细胞上进行的。我们研究了 Ang1-7 在 PNT1A 细胞经过 24 或 48 小时处理后对其生物学特性的影响。使用血管紧张素受体的选择性拮抗剂可以评估介导 Ang1-7 作用的受体。我们的数据清楚地表明,Ang1-7 可以通过抑制 PI3K 轴和调节 NF-κB 基因家族的表达来减少 PNT1A 细胞的增殖和上皮-间充质转化。此外,它通过抑制 VEGF 表达和 MMPs 激活以及调节 ERα 和 ERβ 的水平,来抵抗前列腺细胞中的氧化应激和炎症。另一方面,这种七肽通过改变抗凋亡和促凋亡成员的表达以及 AR 表达的代偿性上调来促进细胞存活。总之,这些结果证实了前列腺中局部 RAS 和甾体激素受体途径的各种成分之间存在复杂的依赖网络。此外,还表明 ACE2/Ang1-7/MAS 途径作为预防和治疗前列腺疾病的新的治疗靶点的可能性。