Xiaosi Hong, Leiqin Cai, Lanlan Li, Dinghao Zheng, Jianghong Lin, Zhuoxian Liang, Wan Fu, Diefei Liang, Tingting Zeng, Kan Sun, Wei Wang, Sifan Chen, Meng Ren, Li Yan
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引用次数: 0
摘要
角质细胞和成纤维细胞功能障碍是糖尿病伤口延迟愈合的原因之一。细胞外小泡（sEV）是细胞间通信的关键介质，与多种疾病的发病机制有关。最近的研究结果表明，来自高葡萄糖处理的角质形成细胞（HaCaT-HG-sEV）的sEV可以转运LINC01435，抑制HUVECs的管形成和迁移，从而延迟伤口愈合。本研究旨在阐明糖尿病伤口愈合过程中角质形成细胞与成纤维细胞之间与 sEV 相关的交流机制。HaCaT-HG-sEV 处理和 LINC01435 过表达可显著降低成纤维细胞胶原蛋白水平和迁移能力，但可显著增加成纤维细胞自噬。然而，用自噬抑制剂处理可抑制 LINC01435 过表达引起的成纤维细胞胶原蛋白水平下降。在糖尿病小鼠中，HaCaT-HG-sEV 处理可降低胶原蛋白水平，并增加伤口部位自噬相关蛋白 Beclin-1 和 LC3 的表达，从而延缓伤口愈合。最终，角质形成细胞衍生 sEV 中的 LINC01435 激活了成纤维细胞的自噬，减少了成纤维细胞胶原蛋白的合成，从而导致糖尿病伤口愈合受损。
Keratinocyte-derived small extracellular vesicles delay diabetic wound healing by triggering fibroblasts autophagy.
Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.
期刊介绍：
Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders.
The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications.
Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics:
-Dysregulation of hormone receptors and signal transduction
-Contribution of gene variants and gene regulatory processes
-Impairment of intermediary metabolism at the cellular level
-Secretion and metabolism of peptides and other factors that mediate cellular crosstalk
-Therapeutic strategies for managing metabolic diseases
Special issues dedicated to topics in the field will be published regularly.
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