RESULTS: Here, we report for the first time that GMFB and SUMO1 are markedly increased in retinal pigment epithelial (RPE) cells at the early stage of diabetes mellitus (DM) under hyperglycemia. The GMFΒ protein could be mono-SUMOylated by SUMO1 at the K20, K35, K58 or K97 sites. SUMOylation of GMFB led to its increased protein stability and subcellular translocation. Furthermore, deSUMOylation of GMFΒ downregulates multiple signaling pathways, including the Jak-STAT signaling pathway, p38 pathway and NF-kappa B signaling pathway.
CONCLUSIONS: This work provides novel insight into the role of SUMOylated GMFB in RPE cells and provides a novel therapeutic target for diabetic retinopathy (DR).
结果:这里,我们首次报道了糖尿病(DM)在高血糖早期视网膜色素上皮(RPE)细胞中GMFB和SUMO1的显着增加。GMFΒ蛋白可以在K20、K35、K58或K97位点被SUMO1单-SUMO化。GMFB的SUMO化导致其增加的蛋白质稳定性和亚细胞易位。此外,GMFΒ的去SUMO化下调多个信号通路,包括Jak-STAT信号通路,p38通路和NF-κB信号通路。
结论:这项工作提供了对SUMO化GMFB在RPE细胞中的作用的新见解,并为糖尿病性视网膜病变(DR)提供了新的治疗靶标。