GPR124在急性肾损伤中的作用及机制

Acute renal injury (AKI) is one of the most important risk factors for chronic kidney disease and end-stage renal disease, in which tubular epithelial cells injury plays the crucial role. GPR124, an orphan adhesion G protein-coupled receptor (GPCR)，plays significant roles in angiogenesis and tumor genesis. However, its role in the pathogenesis of AKI and underlying mechanisms still remain unknown.Our preliminary studies showed that GPR124 was significantly decreased in kidney after AKI,which aggravated inflammatory cells infiltration and promoted the renal injury. GPR124 was significantly decreased in renal tubular epithelial cells after glucose and oxygen deprivation treatment. Overexpression of GPR124 could significantly alleviate the secretion of inflammatory cytokines and reduce apoptosis of renal tubular epithelial cells. Mechanismly, gene sequencing technology indicated that GPR124 may function via the IDO2 signaling pathway,which need further elucidated.Therefore, the present study is designed to verify the function of GPR124 in AKI both in vitro and in vivo by use of the Cre-loxp technique to construct renal tubular epithelial cells-specific GPR124 deletion mouse and other techniques like adenovirus transfection and immunofluorescence technique.Our study intend to enrich the knowledge of the biological function of GPR124 in renal tubular epithelial cells and acute renal injury. Our study will provide a new putative target for the prevention and treatment of AKI which will have important theoretical significance and potential application value.

急性肾损伤（AKI）是造成慢性肾脏病及终末期肾病的重要危险因素，肾小管上皮细胞损伤在其中发挥关键作用。GPR124是粘附类G蛋白偶联受体家族成员之一，在血管生成及肿瘤等领域扮演重要角色，但其在AKI中的作用尚不清楚。我们前期工作首次证实GPR124在AKI小鼠肾脏组织中表达显著降低，并与肾小管上皮细胞损伤相关；同时基因测序提示GPR124对IDO2分子具有调控作用，但其调控机制及其在AKI肾小管损伤中的作用仍需深入阐明。为此，本课题将以GPR124为中心，通过Cre-loxp技术构建近曲肾小管上皮细胞特异性GPR124基因敲除小鼠，运用细胞生物学等方法深入探讨GPR124在AKI中的作用及其通过IDO2通路调控肾小管上皮细胞损伤的分子机制，并对以肾脏局部过表达GPR124作为AKI治疗策略进行初步探讨，为急性肾损伤的防治提供新的靶点和思路，具有重要理论意义。

急性肾损伤（AKI）是造成慢性肾脏病及终末期肾病的重要危险因素，肾小管上皮细胞损伤在其中发挥关键作用。GPR124是粘附类G蛋白偶联受体家族成员之一，在血管生成及肿瘤等领域扮演重要角色，但其在AKI中的作用尚不清楚。我们前期工作首次证实GPR124在AKI小鼠肾脏组织中表达显著降低，并与肾小管上皮细胞损伤相关；同时基因测序提示GPR124对IDO2分子具有调控作用，但其调控机制及其在AKI肾小管损伤中的作用仍需深入阐明。为此，本课题将以GPR124为中心，通过Cre-loxp技术构建近曲肾小管上皮细胞特异性GPR124基因敲除小鼠，运用细胞生物学等方法深入探讨GPR124在AKI中的作用及其通过IDO2通路调控肾小管上皮细胞损伤的分子机制，并对以肾脏局部过表达GPR124作为AKI治疗策略进行初步探讨，为急性肾损伤的防治提供新的靶点和思路，具有重要理论意义。