Yinji Luo, Qijie Guo, Chang Liu, Yuxuan Zheng, Yichong Wang, Bin Wang
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引用次数: 0
Abstract
Aims: Diabetic foot ulcers (DFUs) cause prominent morbidity and mortality. Adipose mesenchymal stem cell (ASC)-derived extracellular vesicles (EVs) show property in facilitating diabetic wound healing, and we explored their role in DFU rats.
Methods: ASCs were cultured in vitro, passaged and then identified by flow cytometry and induction of osteogenic/adipogenic differentiation. ASC-EVs were extracted and identified. DFU rat model was treated with ASC-EVs. High glucose (HG)-induced rat dermal fibroblasts were treated with ASC-EVs or 3-MA and sh-PINK1 plasmid in vitro. Wound healing was observed. Histological changes, inflammatory cytokines (TNF-α, IL-1β), and α-SMA and p21 double-positive cell level were assessed by HE staining, ELISA, and immunofluorescence. Mitochondrial membrane potential (MMP), cell viability and senescence, and ROS production in cells were assessed by fluorescence dye JC-1, CCK-8, SA-β-gal staining, and ROS kit. p21, LC3II/I, p62, PINK1 and parkin protein levels were determined by Western blot.
Results: DFU rats had slow wound healing and elevated levels of IL-1β, TNF-α, α-SMA and p21 double-positive cells, and SA-β-gal, while HG-induced cells had weakened viability, elevated ROS, SA-β-gal, p21 and p62 protein levels, and decreased LC3II/I, PINK1 and parkin protein levels and MMP, which were reversed by ASC-EVs. HG inhibited mitophagy by suppressing the PINK1/parkin pathway to accelerate dermal fibroblast senescence. The PINK1/parkin pathway inhibition partly mitigated the effect of ASC-EVs. ASC-EVs promoted mitophagy by activating the PINK1/parkin pathway in vivo.
Conclusions: ASC-EVs mediated mitophagy by activating the PINK1/parkin pathway, thereby impeding HG-induced rat dermal fibroblast senescence and promoting wound healing in DFU rats.
期刊介绍：
Acta Diabetologica is a journal that publishes reports of experimental and clinical research on diabetes mellitus and related metabolic diseases. Original contributions on biochemical, physiological, pathophysiological and clinical aspects of research on diabetes and metabolic diseases are welcome. Reports are published in the form of original articles, short communications and letters to the editor. Invited reviews and editorials are also published. A Methodology forum, which publishes contributions on methodological aspects of diabetes in vivo and in vitro, is also available. The Editor-in-chief will be pleased to consider articles describing new techniques (e.g., new transplantation methods, metabolic models), of innovative importance in the field of diabetes/metabolism. Finally, workshop reports are also welcome in Acta Diabetologica.
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