MicroRNA-31 Regulates Immunosuppression in Ang II (Angiotensin II)–induced Hypertension by Targeting Ppp6C (Protein Phosphatase 6c)

作者：Xiangxiao Li, Wei Cai, Wenda Xi, Weihong Sun, Weili Shen, Tong Wei, Xiaohui Chen, Libo Sun, Hong Zhou, Yang Sun, Wendong Chen, Pingjin Gao, Honglin Wang, Qun Li · 发表于：Hypertension · 年份：2019 · DOI：10.1161/hypertensionaha.118.12319 · 被引用次数：31 · 研究领域：MicroRNA in disease regulation、Cancer-related molecular mechanisms research、IL-33, ST2, and ILC Pathways

Regulatory T cells (T reg cells) play important roles in hypertension and organ damages. MicroRNA-31 (miR-31) is a critical regulator for T reg cell generation. However, the role of miR-31 in hypertension has not been elucidated. We aim to study the functionality of miR-31 and the detailed mechanism in Ang II (Angiotensin II)–induced hypertensive mouse model. We found: In vitro, miR-31 expression was higher in T helper 17 cells and lower in T reg cells than that of naïve T cells. The genetic deficiency of miR-31 promoted T reg cell differentiation, whereas no impact on T helper 17 cells differentiation. Ang II–induced hypertension resulted in increased expression of miR-31 in the aorta, splenic CD4 + T cells, and kidney leukocytes. MiR-31 deficiency strikingly decreased systolic blood pressure and diastolic blood pressure and attenuated renal and vascular damage. MiR-31 deletion altered the accumulation of T reg cells and macrophages and expression of inflammatory cytokines in kidneys in Ang II–induced hypertensive mice. Ang II treatment reduced the levels of anti-inflammatory cytokines and increased proinflammatory cytokines in plasma that were blunted by the miR-31 deletion. Ppp6C (protein phosphatase 6c; a direct target of miR-31) specific deletion in T reg cells led to marked impairment of T reg cell induction, increased Ang II–induced blood pressure elevation, and organ damage in mice. In conclusion, we provided novel evidence of miR-31 as an emerging key posttranscripti...