Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Vascular Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Endocrinol (Lausanne). 2023 Oct 19;14:1237048. doi: 10.3389/fendo.2023.1237048. eCollection 2023.
Impaired diabetic wound healing is an important issue in diabetic complications. Proliferation and migration of keratinocytes are major processes of skin wound repair after injury. However, hyperkeratosis can affect the speed of wound healing. Based on the results of preliminary experiments on increased KRT17 expression after high glucose stimulation of human skin tissue cells, a cell model of human immortalized keratinocyte (HaCaT) stimulation with different concentrations of KRT17 was established , and the promotion in cell proliferation and migration were discovered. KRT17 silencing promoted diabetic wound healing in the db/db diabetic wound model. Transcriptome sequencing (RNA-seq) was performed on HaCaT cells after KRT17 stimulation, and analysis showed significant enrichment in the PI3K-AKT signaling pathway, in which the regulation of cell c-MYB mRNA, a key molecule regulating cell proliferation and migration, was significantly upregulated. assays showed increased c-MYB expression and enhanced pAKT activity after HaCaT cell stimulation by KRT17. We speculate that KRT17 is upregulated under high glucose and promotes keratinocyte proliferation and migration caused hyperkeratosis, through the c-MYB/PI3K-AKT pathway, contributing to delayed wound healing.
糖尿病患者的伤口愈合受损是糖尿病并发症的一个重要问题。角朊细胞的增殖和迁移是皮肤损伤后修复的主要过程。然而，过度角化会影响伤口愈合的速度。基于高糖刺激人皮肤组织细胞后 KRT17 表达增加的初步实验结果，建立了不同浓度 KRT17 刺激人永生化角质形成细胞（HaCaT）的细胞模型，发现细胞增殖和迁移得到促进。KRT17 沉默促进了 db/db 糖尿病伤口模型中的糖尿病伤口愈合。对 KRT17 刺激后的 HaCaT 细胞进行转录组测序（RNA-seq）分析，结果表明 PI3K-AKT 信号通路显著富集，其中调节细胞增殖和迁移的关键分子细胞 c-MYB mRNA 的调节显著上调。测定表明，KRT17 刺激 HaCaT 细胞后 c-MYB 表达增加，pAKT 活性增强。我们推测高糖下 KRT17 的上调通过 c-MYB/PI3K-AKT 通路促进角质形成细胞增殖和迁移导致过度角化，从而导致伤口愈合延迟。
