环状RNA-GLIS3介导巨噬细胞极化在糖尿病性视网膜微血管病变中的作用及其机制研究

Macrophage polarization is a process that macrophages exert different functions according to surrounding micro-environment. Macrophages commonly exist in two distinct subsets: classically activated M1 macrophages and alternatively activated M2 macrophages. The polarization of macrophages occurs in the situation such as inflammation, vascular dysfunction and immunity. It plays key roles in many diseases. Circular RNAs (circRNAs) are a class of important genetic elements that regulate a wide range of physiological and pathological processes. To date, the role of circRNAs mediated macrophage polarization in diabetic retinas is still unclear. Our previous study has revealed that cGLIS3 is up-regulated in M1 macrophages and diabetic retinas. However, the mechanism of cGLIS3 regulating macrophage polarization remains unknown. Herein, we will detect cGLIS3 expression pattern in macrophages or retinas upon high glucose stress at different time points, clarify the role of cGLIS3 in macrophage polarization and vascular dysfunction through in vitro or in vivo intervention of cGLIS3 expression, and reveal the molecular mechanism of cGLIS3-mediated macrophage polarization. This study will provide novel insights into the mechanism underlying macrophage polarization and a new target for treating diabetes mellitus-induced microvascular dysfunction.

巨噬细胞极化是指巨噬细胞随所处微环境的变化极化为不同的表型，主要分为经典激活型（M1型）和替代激活型（M2型），调控机体炎症、血管功能和免疫等过程。环状RNA（circRNAs）是一类重要的基因元件，调控众多生理和病理过程。然而，circRNAs能否调控糖尿病性视网膜组织中巨噬细胞极化尚未有报道。预实验发现，在M1型巨噬细胞和糖尿病动物视网膜中cGLIS3表达显著上调，但cGLIS3调控巨噬细胞极化的机制仍不清楚。本项目拟建立巨噬细胞极化模型和糖尿病小鼠模型，从在体和离体水平分析巨噬细胞极化与cGLIS3的表达规律；基于对cGLIS3的表达干预，明确cGLIS3对巨噬细胞极化和微血管病变的调控作用；基于生物信息学和分子生物学技术，阐明cGLIS3调控巨噬细胞极化的分子机制。研究有望揭示巨噬细胞极化的调控新机制，为糖尿病视网膜病变治疗提供新靶点。

巨噬细胞极化是指巨噬细胞随所处微环境的变化极化为不同的表型，主要分为经典激活型 (M1型)和替代激活型(M2型)，调控机体炎症、血管功能和免疫等过程。环状RNA(circRNA s)是一类重要的基因元件，调控众多生理和病理过程。然而，circRNAs能否调控糖尿病性视 网膜组织中巨噬细胞极化尚未有报道。预实验发现，在M1型巨噬细胞和糖尿病动物视网膜中cG LIS3表达显著上调，但cGLIS3调控巨噬细胞极化的机制仍不清楚。本项目拟建立巨噬细胞极化模型和糖尿病小鼠模型，从在体和离体水平分析巨噬细胞极化与cGLIS3的表达规律;基于对cG LIS3的表达干预，明确cGLIS3对巨噬细胞极化和微血管病变的调控作用;基于生物信息学和分子生物学技术，阐明cGLIS3调控巨噬细胞极化的分子机制。研究旨在揭示巨噬细胞极化的调控新机制，为糖尿病视网膜病变治疗提供新靶点。