Previous studies found that hypoxic pretreatment of endothelial progenitor cells (EPCs) prior to transplantation had a greater therapeutic effect than untreated EPCs in promoting diabetic wound healing. However, the exact mechanism is uncertain. Here, circRNA expression in EPCs after hypoxic treatment was investigated. High-throughput sequencing was used to assess abnormal expression by EPCs of circular RNAs (circRNAs) following hypoxic pretreatment. Additionally, an in vivo full-thickness skin defect mouse model was used to assess the effects of transplanted EPCs on diabetic wound closure. Subsequently, the regulatory mechanism and targets were studied. The results showed that circ-Klhl8 overexpression suppressed hyper glucose-induced endothelial cell damage by activating autophagy. MiR-212-3p and SIRT5 were identified as the downstream targets of circ-Klhl8. Circ-Klhl8 overexpression promoted skin wound healing by regulating SIRT5-mediated autophagy. In conclusion, the study found that circ-Klhl8 overexpression increased the EPC therapeutic effect in promoting diabetic wound healing by targeting the miR-212-3p/SIRT5 axis.

先前的研究发现，移植前内皮祖细胞（EPCs）的缺氧预处理比未处理的EPCs在促进糖尿病伤口愈合方面具有更大的治疗效果。然而，确切的机制尚不确定。在这里，研究了缺氧处理后 EPCs 中 circRNA 的表达。高通量测序用于评估缺氧预处理后环状 RNA (circRNA) 的 EPC 异常表达。此外，体内使用全层皮肤缺损小鼠模型评估移植的 EPCs 对糖尿病伤口闭合的影响。随后，对其调控机制和靶点进行了研究。结果表明，circ-Klhl8 过表达通过激活自噬来抑制高糖诱导的内皮细胞损伤。MiR-212-3p 和 SIRT5 被确定为 circ-Klhl8 的下游目标。Circ-Klhl8 过表达通过调节 SIRT5 介导的自噬促进皮肤伤口愈合。总之，该研究发现circ-Klhl8过表达通过靶向miR-212-3p/SIRT5轴增加了EPC促进糖尿病伤口愈合的治疗效果。