Abstract 089: Response Gene To Complement 32 Is Involved In Glucose Metabolism Disorder In Endothelial Cells And Mediated By P53

Abstract

Response gene to complement 32 (RGC-32) was considered as an apoptosis-promoting factor. To explore the novel functions of RGC-32, a DNA array analysis was performed in Human Microvascular Endothelial Cells (HMEC) treated with SiRNA, which showed that glucose metabolism was one of most dramatically changed biological process. qPCR analysis also proved that many glucose metabolism related genes were changed dramatically in RGC32 o/e HMEC, one of which was Insulin-like growth factor binding protein 4(IGFBP4). We propose that RGC-32 may be a potential factor involved in the cycle of endothelial glucose metabolism besides glucose induced apoptosis. Then we found that expression of RGC-32 was dramatically increased in mice hearts and adipose tissue after high fat diet treatment, as well as in HMEC after high glucose (30mM) treatment. In high fat diet treated endothelial specific RGC-32 transgenic mice (VE-Cad/RGC-32), decreases in area under the curve (AUC) of glucose tolerance test were observed when compared to their wild type littermates. Upregulated P53 and downregulated IGFBP4 mRNA expression level were also observed in the heart of VE-Cad/RGC-32 mice.Furthermore, we found that P53 was upregulated in RGC-32 o/e HMEC and blocking of p53 was able to decrease the RGC-32-related induction of apoptotic cells. We also observed that RGC-32 can not only decrease IGFBP4 but also reverse the decrease of IGFBP4 in high glucose or insulin condition. Interestingly, after treated the cells with pifithrin-a, a specific P53 inhibitor, decreased IGFBP4 by RGC-32 was rescued. These results demonstrate that RGC-32 may have some kind of connections with glucose metabolism besides its well-known apoptosis-promoting characters and P53 may be a mediator of RGC-32 related glucose metabolism disorder as well as apoptosis.These findings will provide some clues for novel insights into the functions of RGC-32.