Wu Yuxi, Wu Xiaoying, Wang Jiahuan, Chen Sifan, Chen Hongxing, Liu Jing, Zeng Tingting, Hu Mengdie, Liang Ying, Sun Kan, Yang Chuan, Yan Li, Ren Meng
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Department of Endocrinology, National Center of Gerontology, Beijing Hospital, Peking University Fifth School of Clinical Medicine, Beijing, China.
Lab Invest. 2023 Mar;103(3):100019. doi: 10.1016/j.labinv.2022.100019. Epub 2023 Jan 10.
Accurate communication between fibroblasts and keratinocytes is crucial for diabetic wound healing. Extracellular vesicles are being explored as essential mediators of intercellular communication in the skin. However, the mechanisms underlying wound healing mediated by fibroblast-derived extracellular vesicles (Fib-EVs) remain unclear. The present study evaluated the role of long noncoding RNA upregulated in diabetic skin (lnc-URIDS) packed in Fib-EVs in the wound healing of streptozotocin-induced diabetes and the potential mechanisms of the effects. We demonstrated that high glucose induced the enrichment of lnc-URIDS in Fib-EVs, facilitated the transfer of lnc-URIDS to primary rat epidermal keratinocytes, and increased the expression of matrix metalloproteinase-9. Mechanistically, the binding of lnc-URIDS to YTH domain family protein-2 enhanced the degradation of YTH domain family protein-2 in the lysosomes, which increased the translational activity of the messenger RNA of matrix metalloproteinase-9 and ultimately induced the degradation of collagen for wound healing. The results provided an insight into the crosstalk and cooperation between fibroblasts and keratinocytes in collagen homeostasis in diabetic wounds and clarified the mechanism by which lnc-URIDS degrades collagen for diabetic wound healing.
成纤维细胞与角质形成细胞之间的准确通讯对糖尿病伤口愈合至关重要。细胞外囊泡正被探索为皮肤细胞间通讯的重要介质。然而，成纤维细胞衍生的细胞外囊泡（Fib-EVs）介导伤口愈合的潜在机制仍不清楚。本研究评估了Fib-EVs中包裹的长链非编码RNA上调在糖尿病皮肤（lnc-URIDS）中对链脲佐菌素诱导的糖尿病伤口愈合的作用及其影响的潜在机制。我们证明高糖诱导lnc-URIDS在Fib-EVs中富集，促进lnc-URIDS向原代大鼠表皮角质形成细胞的转移，并增加基质金属蛋白酶-9的表达。机制上，lnc-URIDS与YTH结构域家族蛋白-2的结合增强了YTH结构域家族蛋白-2在溶酶体中的降解，这增加了基质金属蛋白酶-9信使RNA的翻译活性，并最终诱导胶原蛋白降解以促进伤口愈合。这些结果为深入了解糖尿病伤口中胶原蛋白稳态下成纤维细胞与角质形成细胞之间的相互作用和合作提供了思路，并阐明了lnc-URIDS降解胶原蛋白促进糖尿病伤口愈合的机制。
