氧化应激
伤口愈合
炎症
活性氧
PI3K/AKT/mTOR通路
脂质过氧化
医学
蛋白激酶B
糖尿病
细胞凋亡
药理学
癌症研究
化学
免疫学
细胞生物学
生物
内科学
内分泌学
生物化学
作者
Shuangwen Li,Yuan Li,Zanyi Wu,Zhongming Wu,Hongjuan Fang
出处
期刊:American Journal of Physiology-endocrinology and Metabolism
[American Physiological Society]
日期:2021-10-01
卷期号:321 (4): E509-E520
被引量:39
标识
DOI:10.1152/ajpendo.00042.2021
摘要
Impaired wound healing is a major complication of diabetes and involves sustained inflammation and oxidative stress at the wound site. Here, we investigated the potential involvement of ferroptosis, a newly discovered form of cell death characterized by iron-dependent accumulation of lipid peroxides in the pathogenesis of diabetic wound healing. Fibroblasts and vascular endothelial cells exposed to high glucose concentrations in vitro contained elevated levels of reactive oxygen species (ROS), lipid peroxidation products, and ferroptosis-associated proteins and displayed reduced survival and migration. These effects of high glucose were all significantly reduced by treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Similarly, in a rat model of diabetes, direct application of Fer-1 to the wound site reduced the expression of oxidative stress and inflammation markers and accelerated wound healing via activation of the anti-inflammatory phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Our results implicate ferroptosis in wound healing and identify a potential new therapeutic target for difficult-to-treat diabetic wounds.NEW & NOTEWORTHY Ferroptosis-related characteristic changes were found in diabetic wound models. Inhibition of ferroptosis improved inflammatory infiltration of diabetic wounds. PI3K/AKT signal pathway was rescued by restraining of ferroptosis. Mitigation of ferroptosis in diabetic wound promoted the wound healing.
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