Autophagosomes Defeat Ferroptosis by Decreasing Generation and Increasing Discharge of Free Fe2+ in Skin Repair Cells to Accelerate Diabetic Wound Healing

被引：41

作者：

Cui, Shengnan ^{[1
]}

Liu, Xi ^{[2
]}

Liu, Yong ^{[3
]}

Hu, Wenzhi ^{[2
]}

Ma, Kui ^{[2
]}

Huang, Qilin ^{[4
]}

Chu, Ziqiang ^{[2
,5
]}

Tian, Lige ^{[4
]}

Meng, Sheng ^{[2
]}

Su, Jianlong ^{[2
]}

Zhang, Wenhua ^{[2
]}

Li, Haihong ^{[6
]}

Fu, Xiaobing ^{[2
,5
,7
,8
]}

Zhang, Cuiping ^{[2
,5
,7
,8
]}

机构：

[1] China Acad Chinese Med Sci, Xiyuan Hosp, Dept Dermatol, Beijing 100091, Peoples R China

[2] Chinese Peoples Liberat Army Gen Hosp, Res Ctr Tissue Repair & Regenerat, Med Innovat Res Div, Med Ctr 4, Beijing 100048, Peoples R China

[3] Shaanxi Prov Hosp Chinese Med, Dept Dermatol, Xian 710003, Peoples R China

[4] Tianjin Med Univ, Chinese PLA Gen Hosp, Dept Med Ctr 4, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China

[5] Chinese Peoples Liberat Army Gen Hosp, Dept Med Ctr 1, Chinese PLA Med Sch, 28 Fuxing Rd, Beijing 100853, Peoples R China

[6] Southern Univ Sci & Technol, Southern Univ Sci & Technol Hosp, Inst Wound Repair & Regenerat Med, Sch Med,Dept Wound Repair, Shenzhen 518055, Peoples R China

[7] Chinese Acad Med Sci, Res Unit Trauma Care Tissue Repair & Regenerat, 2019RU051,51 Fucheng Rd, Beijing 100048, Peoples R China

[8] Beijing Key Res Lab Skin Injury Repair & Regenerat, 51 Fucheng Rd, Beijing 100048, Peoples R China

来源：

ADVANCED SCIENCE | 2023年 / 10卷 / 25期

关键词：

autophagosomes; diabetic wounds; endoplasmic reticulum stress; exosomes; ferroptosis; SMALL EXTRACELLULAR VESICLE; IRON; SECRETION; PROTECTS; FERRITIN; PATHWAY; STRESS;

D O I：

10.1002/advs.202300414

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Ferroptosis plays an essential role in the development of diabetes and its complications, suggesting potential therapeutic strategies targeting ferroptosis. Secretory autophagosomes (SAPs) carrying cytoplasmic cargoes have been recognized as novel nano-warrior to defeat diseases. Here, it is hypothesized that SAPs derived from human umbilical vein endothelial cells (HUVECs) can restore the function of skin repair cells by inhibiting ferroptosis to promote diabetic wound healing. High glucose (HG)-caused ferroptosis in human dermal fibroblasts (HDFs) is observed in vitro, which results in impaired cellular function. SAPs successfully inhibit ferroptosis in HG-HDFs, thereby improving their proliferation and migration. Further research show that the inhibitory effect of SAPs on ferroptosis resulted from a decrease in endoplasmic reticulum (ER) stress-regulated generation of free ferrous ions (Fe2+) in HG-HDFs and an increase in exosome release to discharge free Fe2+ from HG-HDFs. Additionally, SAPs promote the proliferation, migration, and tube formation of HG-HUVECs. Then the SAPs are loaded into gelatin-methacryloyl (GelMA) hydrogels to fabricate functional wound dressings. The results demonstrate the therapeutic effect of Gel-SAPs on diabetic wounds by restoring the normal behavior of skin repair cells. These findings suggest a promising SAP-based strategy for the treatment of ferroptosis-associated diseases.

引用

页数：17

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