miR-126调节对糖尿病环境下内皮祖细胞归巢的影响和机制

CXCR4表达下调致 SDF-1α/CXCR4调控障碍是糖尿病机体EPCs归巢损伤的重要机制。前期我们发现，糖尿病患者EPCs上miR-126低表达降低EPCs迁移、增殖，增加凋亡；通过靶基因spred-1调控多条信号通路。本研究将论证miR-126通过上调EPCs上CXCR4表达，从而促进SDF-1α/CXCR4信号通路调控的糖尿病机体EPCs归巢的作用和相关机制。我们拟以高血糖EPCs为研究对象，正负两方面探讨miR-126对EPCs上CXCR4表达的影响及其在SDF-1α诱导的EPCs定向迁移中的作用和信号通路；明确2型糖尿病环境对EPCs上miR-126表达和转录后调控的影响；并在糖尿病GK大鼠体内验证。本研究将为揭示糖尿病机体EPCs归巢的转录后调控机制提供新的思路。

Down-regulated expression of CXCR4 in EPCs and the subsequent SDF-1α/CXCR4 signal transcriptional disorder are currently recognized as a major mechanism responsible for impaired EPCs homing in diabetic patients.Our previous study showed that miR-126 is down-regulated in EPCs in diabetic patients and miR-126 inhibits EPCs proliferation, migration, and promotes EPCs apoptosis. Spred-1 is identified as one of the target genes of miR-126. MiR-126 regulates EPCs function by several pathways, all of them depend on Spred-1. In this study, we establish a series of protocols to elucidate the expression of miR-126 in EPCs, to explore the effects and mechanism of miR-126 on CXCR4 expression and SDF-1a-induced EPCs migration, to clarify mir-126's effect on the post-transcriptional regulation of SDF-1a/CXCR4 and SDF-1α-induced EPCs mobilization in type-II diabetic patients, and to further testify these effects in vivo in diabetic GK rat.