The role of Q10 engineering mesenchymal stem cell-derived exosomes in inhibiting ferroptosis for diabetic wound healing

被引：0
作者：
Yang, Ronghua [1 ]
Zhou, Sitong [2 ]
Huang, Jie [1 ]
Kang, Deni [1 ]
Chen, Yao [1 ]
Wang, Xinyi [1 ]
Shi, Yan [3 ]
Wang, Zhengguang [4 ]
机构：
[1] South China Univ Technol, Guangzhou Med Univ, Guangzhou Peoples Hosp 1, Dept Burn & Plast Surg, Panfu Rd, Guangzhou 510180, Guangdong, Peoples R China
[2] First Peoples Hosp Foshan, Dept Dermatol, Lingnan North Rd, Guangzhou 528000, Peoples R China
[3] Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Coll, Med Ctr Burn Plast & Wound Repair,Dept Plast, Yongwaizheng Rd, Nanchang 330006, Jiangxi, Peoples R China
[4] Peking Univ Third Hosp, Dept Orthopaed, 49 North Garden Rd, Beijing 100191, Peoples R China
来源：
BURNS & TRAUMA | 2024年 / 12卷
基金：
中国国家自然科学基金;
关键词：
Ferroptosis; Exosomes; Coenzyme Q10; ACSL4; Diabetic wound healing; Keratinocytes; Mesenchymal stem cells; Keratinocyte;
D O I：
10.1093/burnst/tkae054
中图分类号：
R4 [临床医学];
学科分类号：
1002 ; 100602 ;
摘要：
Background: Ferroptosis plays an essential role in the development of diabetes and its complications, suggesting its potential as a therapeutic target. Stem cell-derived extracellular vesicles (EVs) are increasingly being developed as nano-scale drug carriers. The aim of this study was to determine the role of ferroptosis in the pathogenesis of diabetic wound healing and evaluate the therapeutic effects of coenzyme Q10 (Q10)- stimulated exosmes derived from mesenchymal stem cells (MSCs). Methods: Human keratinocytes (HaCaTs) were exposed to high glucose (HG) conditions in vitro to mimic diabetic conditions, and the ferroptosis markers and expression level of acyl-coenzyme A synthase long-chain family member 4 (ACSL4) were determined. Exosomes were isolated from control and Q10-primed umbilical cord mesenchymal stem cells (huMSCs) and characterized by tramsmission electron microscopy and immunofluorescence staining. The HG-treated HaCaTs were cultured in the presence of exosomes derived from Q10-treated huMSCs (Q10Exo) and their in vitro migratory capacity was analyzed. Results: Q10-Exo significantly improved keratinocyte viability and inhibited ferroptosis in vitro. miR-548ai and miR-660 were upregulated in the Q10-Exo and taken up by HaCaT cells. Furthermore, miR-548ai and miR-660 mimics downregulated ACSL4-inhibited ferroptosis in the HG-treated HaCaT cells and enhanced their proliferation and migration. However, simultaneous upregulation of ACSL4 reversed their effects. Q10-Exo also accelerated diabetic wound healing in a mouse model by inhibiting ACSL4-induced ferroptosis. Conclusions: Q10-Exo promoted the proliferation and migration of keratinocytes and inhibited ferroptosis under hyperglycemic conditions by delivering miR-548ai and miR-660. Q10-Exo also enhanced cutaneous wound healing in diabetic mice by repressing ACSL4-mediated ferroptosis. [GRAPHICS]
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页数：16
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  • [1] Singh N, Armstrong DG, Lipsky BA., Preventing foot ulcers in patients with diabetes, JAMA, 293, pp. 217-228, (2005)
  • [2] Shi Y, Wang S, Zhang W, Zhu Y, Fan Z, Huang Y., Et al., Bone marrow mesenchymal stem cells facilitate diabetic wound healing through the restoration of epidermal cell autophagy via the HIF-1α/TGF-β1/SMAD pathway, Stem Cell Res Ther, 13, (2022)
  • [3] Guan Y, Niu H, Liu Z, Dang Y, Shen J, Zayed M., Et al., Sustained oxygenation accelerates diabetic wound healing by promoting epithelialization and angiogenesis and decreasing inflammation, Sci Adv, 7, (2021)
  • [4] Liu Y, Shi Y, Zhu J, Chen XD, Yang RH, Shu B., Et al., Study on the effect of the five-in-one comprehensive limb salvage Technologies of Treating Severe Diabetic Foot, Advances in wound care, 9, pp. 676-685, (2020)
  • [5] Long M, Rojo de la Vega M, Wen Q, Bharara M, Jiang T, Zhang R., Et al., An essential role of NRF2 in diabetic wound healing, Diabetes, 65, pp. 780-793, (2016)
  • [6] Fu Y, Liu Y, Song W, Yang D, Wu W, Lin J., Et al., Early monitoring-to-warning internet of things system for emerging infectious diseases via networking of light-triggered point-of-care testing devices, Exploration (Beijing), 3, (2023)
  • [7] Xiong Y, Feng Q, Lu L, Qiu X, Knoedler S, Panayi AC., Et al., Metal-organic frameworks and their composites for chronic wound healing: from bench to bedside, Advanced materials (Deerfield Beach, Fla), 36, (2024)
  • [8] Qiang L, Yang S, Cui YH, He YY, Keratinocyte autophagy enables the activation of keratinocytes and fibroblastsand facilitates wound healing, Autophagy, 17, pp. 2128-2143, (2021)
  • [9] Hu SC, Lan CE., High-glucose environment disturbs the physiologic functions of keratinocytes: focusing on diabetic wound healing, J Dermatol Sci, 84, pp. 121-127, (2016)
  • [10] Liang D, Lin WJ, Ren M, Qiu J, Yang C, Wang X., Et al., M(6)a reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin, Autophagy, 18, pp. 1318-1337, (2022)
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