Renin-Angiotensin System (RAS) is an important peptide cascade involved in physiological processes. RAS homeostasis disruption produces several cardiovascular and metabolic disorders, such as arterial hypertension, atherosclerosis, acute myocardial infarct, obesity, diabetes, metabolic syndrome and increases gastrointestinal tract (GIT) cell proliferation. Angiotensin (Ang)-(1-7) peptide is the main RAS counter-regulatory axis effector. It is formed from ACE2 enzyme and acts mainly through Mas receptor (MasR). In this context, the aim of the present study was to evaluate alterations in small intestine morphology and intestinal microbiota composition in MasR knockout C57BL/6 mice. We analyzed glucose tolerance; insulin sensitivity and blood collected for biochemical parameters as well as small intestine tissues samples for immunohistochemistry. mRNA and bacteria gDNA expression evaluation. mRNA expression was evaluated by qRT-PCR for TLR4, PI3K and AKT. The main results showed that Mas-R-knockout mice presented lower body weight. MasR-knockout mice also presented increased fasted blood glucose and total cholesterol with reduced HDL, lower glucose tolerance and impaired insulin sensitivity. Increased intestinal mucosa length, increased intestinal villi, reduced Lieberkühn crypt depth. The increased expression of cell proliferation markers Ki-67 and Cyclin D1 and increased TLR4, PI3K and AKT expressions were observed with augmented Bacteroidetes and decreased amount of Firmicutes. That results suggests that MasR deletion generated changes in intestinal microbiota, possibly due to a lower neutral amino acids absorption followed by a compensatory increase in intestinal villi length associated with disbiosis and LPS overproduction that ultimately lead to proliferation and cell inflammation.

中文翻译：

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血管紧张素-(1-7) 受体 mas 的基因缺失导致肠道绒毛长度的改变，调节 TLR4/PI3K/AKT 并产生微生物群失调

肾素-血管紧张素系统 (RAS) 是参与生理过程的重要肽级联反应。RAS 稳态破坏会导致多种心血管和代谢紊乱，例如动脉高血压、动脉粥样硬化、急性心肌梗塞、肥胖症、糖尿病、代谢综合征，并增加胃肠道 (GIT) 细胞增殖。血管紧张素 (Ang)-(1-7) 肽是主要的 RAS 反调节轴效应物。它由 ACE2 酶形成，主要通过 Mas 受体 (MasR) 起作用。在这种情况下，本研究的目的是评估 MasR 敲除 C57BL/6 小鼠小肠形态和肠道微生物群组成的变化。我们分析了葡萄糖耐量；为生化参数收集胰岛素敏感性和血液以及用于免疫组织化学的小肠组织样本。mRNA 和细菌 gDNA 表达评估。通过 qRT-PCR 评估 TLR4、PI3K 和 AKT 的 mRNA 表达。主要结果表明，Mas-R 基因敲除小鼠的体重较低。MasR 基因敲除小鼠还表现出空腹血糖和总胆固醇升高，HDL 降低，糖耐量降低和胰岛素敏感性受损。肠黏膜长度增加，肠绒毛增加，Lieberkühn 隐窝深度减少。在拟杆菌增加和厚壁菌数量减少的情况下，观察到细胞增殖标志物 Ki-67 和细胞周期蛋白 D1 的表达增加，TLR4、PI3K 和 AKT 的表达增加。结果表明，MasR 缺失导致肠道微生物群发生变化，