Fu Wan, Liang Diefei, Wu Xiaoying, Chen Hongxing, Hong Xiaosi, Wang Jiahuan, Zhu Tianxin, Zeng Tingting, Lin Weijie, Chen Sifan, Yan Li, Ren Meng
Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, China.
iScience. 2022 Mar 1;25(4):104006. doi: 10.1016/j.isci.2022.104006. eCollection 2022 Apr 15.
Abnormal interactions between skin cells play an important role in the dysregulation of diabetic wound recovery. Exosomes are cell-derived lipid nanoparticles that transport messages between cells, and isolating and identifying potential therapeutic noncoding RNAs from exosomes is very important. We demonstrated that treatment with Exos from high glucose-pretreated immortalized human epidermal (HaCaT) cells (HG-Exos) could delay the wound healing process in diabetic mice. Further analysis indicated the Exo-mediated uptake of LINC01435 in recipient human umbilical vein endothelial cells (HUVECs) changes the subcellular localization of the transcription factor Yin Yang 1 (YY1) and cooperates with YY1 to upregulate the expression of histone deacetylases (HDACs)8, resulting in decreased tube formation and ability of HUVECs to migrate, thus angiogenesis was inhibited. These results suggest that LINC01435/YY1/HDAC8 may be an important signaling pathway affecting the recovery of diabetic wounds, which makes it a potential target for the treatment of diabetic foot ulcers.
皮肤细胞之间的异常相互作用在糖尿病伤口愈合失调中起重要作用。外泌体是细胞衍生的脂质纳米颗粒,可在细胞间传递信息,从外泌体中分离和鉴定潜在的治疗性非编码RNA非常重要。我们证明,用高糖预处理的永生化人表皮(HaCaT)细胞来源的外泌体(HG-Exos)处理可延迟糖尿病小鼠的伤口愈合过程。进一步分析表明,外泌体介导的LINC01435在受体人脐静脉内皮细胞(HUVECs)中的摄取改变了转录因子阴阳1(YY1)的亚细胞定位,并与YY1协同上调组蛋白脱乙酰基酶(HDACs)8的表达,导致HUVECs的管形成和迁移能力降低,从而抑制了血管生成。这些结果表明,LINC01435/YY1/HDAC8可能是影响糖尿病伤口愈合的重要信号通路,这使其成为治疗糖尿病足溃疡的潜在靶点。