磷酸酶和张力蛋白同源基因诱导激酶1与糖尿病难愈创面修复的研究进展

Association of Phosphatase and Tensin Homologue-induced Putative Kinase 1 with Refractory Diabetic Wound Healing:a Review

慢性难愈创面已成为糖尿病严重的并发症之一,且缺乏有效的治疗方法。大量研究证实糖尿病创面修复过程中炎性反应、血管形成及基质重塑等事件均与线粒体功能密切相关。磷酸酶和张力蛋白同源基因诱导激酶1(PINK1)是一种丝氨酸/苏氨酸蛋白激酶,主要定位在线粒体。PINK1参与调控线粒体自噬,保护细胞免受氧化应激损害;另外,其在调控炎性反应、促进脂质代谢等事件中发挥重要作用。PINK1基因突变与帕金森综合征发病密切相关。最近的研究显示PINK1可参与调控2型糖尿病的发生和发展进程。本文综述了PINK1参与糖尿病创面修复机制的最新研究进展,希望通过阐明PINK1调控创面修复的作用机制,发现目前该方面研究尚存的问题。现有研究未能揭示创面修复的不同阶段PINK1参与的分子机制与信号转导过程的时序性和交互作用,且目前仍缺乏PINK1调控糖尿病难愈创面修复的体内研究,期待后期进一步的临床研究为糖尿病难愈创面治疗提供更多思路。

Chronic and refractory wounds are serious complications of diabetes mellitus,and have no effective treatments. Numerous studies have confirmed that events such as inflammatory response,angiopoiesis and matrix remodeling are closely related to mitochondrial function during diabetic wound healing. Phosphatase and tensin homologue-induced kinase 1(PINK1) is a serine/threonine protein kinase primarily located in mitochondria,which is involved in regulating mitochondrial autophagy to protect cells from oxidative stress,and plays an important role in regulating inflammatory responses and promoting lipid metabolism. Mutations in the PINK1 gene are closely related to the onset of Parkinson’s syndrome. Recent studies also show that PINK1 may be involved in regulating the development of type 2 diabetes. We gave a description of the mechanism of action of PINK1 in regulating diabetic wound healing after reviewing the latest relevant research,and found that existing studies have failed to reveal the molecular mechanism and the time sequence and interaction of signal transduction process involved by PINK1in different stages of wound healing. Moreover,there is still a lack of in vivo research on PINK1 regulating the healing of refractory diabetic wounds. It is hoped that further clinical research could provide more ideas for the treatment of refractory diabetic wounds.