<br>葡萄籽原花青素通过 p-JNK/FOXO3a/ROS 信号通路调节小鼠内皮细胞的线粒体自噬并促进伤口愈合,Archives of Biochemistry and Biophysics

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葡萄籽原花青素通过 p-JNK/FOXO3a/ROS 信号通路调节小鼠内皮细胞的线粒体自噬并促进伤口愈合
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2023-10-17 , DOI: 10.1016/j.abb.2023.109790
Liuqing Chen ₁ , Li Hao ₂ , Chen Yanshuo ₁ , Wu FangFang ₃ , Chen Daqin ₃ , Xia Weidong ₄ , Xiao Jian ₅ , Chen Shaodong ₂ , Zhang Hongyu ₅ , Xu Ke ₁

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皮肤伤口愈合是一个动态而复杂的过程，涉及多种生理和细胞事件。葡萄籽原花青素（GSP）具有很强的抗氧化和消除氧自由基的作用，并已被证明可以显着促进伤口愈合，但其潜在机制尚不清楚。研究表明，活性氧（ROS）作为诱导线粒体自噬的上游信号，表明 GSP 可以通过信号通路调节线粒体自噬。本研究旨在探讨 GSP 是否通过下调氧化应激来促进伤口愈合来调节线粒体自噬。在体内，GSP 治疗加速了小鼠的伤口愈合、肉芽组织形成、胶原蛋白沉积和血管生成。此外，GSP 通过上调 p-JNK/FOXO3a 蛋白的表达下调 ROS 水平并促进抗氧化蛋白的表达，从而调节线粒体自噬相关蛋白的表达。在体外，4 μg/mL GSP 对细胞没有明显的毒性作用，有效降低了 H2O2 诱导的细胞氧化应激损伤。Western blot 和超氧阴离子荧光探针进一步证实，GSP 通过激活 p-JNK/FOXO3a 蛋白表达，有效降低二氢乙锭含量并上调抗氧化蛋白的表达，从而调节线粒体自噬。综上所述，体外和体内实验的结果为 GSP 促进伤口愈合提供了新的见解。

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Grape seed proanthocyanidins regulate mitophagy of endothelial cells and promote wound healing in mice through p-JNK/FOXO3a/ROS signal pathway

Skin wound healing is a dynamic and complex process that involves multiple physiological and cellular events. Grape seed proanthocyanidins (GSP) have strong anti-oxidation and elimination of oxygen free radicals, and have been shown to significantly promote wound healing, but the underlying mechanism remains unclear. Studies have indicated that reactive oxygen species (ROS) acts as an upstream signal to induce mitophagy, suggesting that GSP can regulate mitophagy through the signal pathway. This study aimed to investigate whether GSP regulates mitophagy by down-regulating oxidative stress to promote wound healing. In vivo, GSP treatment accelerated wound healing, granulation tissue formation, collagen deposition, and angiogenesis in mice. Moreover, GSP down-regulated ROS levels and promoted the expression of antioxidant proteins by up-regulating the expression of p-JNK/FOXO3a protein, thereby regulating the expression of mitophagy-related proteins. In vitro, 4 μg/mL GSP showed no apparent toxic effects on cells and effectively reduce the oxidative stress damage of cells induced by H2O2. Western blot and superoxide anion fluorescence probe further confirmed that GSP effectively reduced Dihydroethidium content and up-regulated the expression of antioxidant proteins by activation of p-JNK/FOXO3a protein expression, thereby regulating mitophagy. Taken together, the findings from in vitro and in vivo experiments provide new insights into the promotion of wound healing by GSP.

更新日期：2023-10-17

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