Role of CD147 in regulating the RSK2/Slug/EMT pathway in diabetic foot ulcer healing.
Role of CD147 in regulating the RSK2/Slug/EMT pathway in diabetic foot ulcer healing.
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DOI：
10.11817/j.issn.1672-7347.2020.200018
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发表时间：
2020-08-28
期刊：
影响因子：
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通讯作者：
Qi, Min
中科院分区：
文献类型：
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作者：
Guo, Jia;Zhang, Jianglin;Qi, Min
目的：糖尿病足溃疡（DFU）是糖尿病的严重并发症，具有较高的截肢率和死亡率。但糖尿病足的治疗效果较差。本研究旨在探讨CD147对DFU上皮间质转化（EMT）过程的影响及分子机制。方法：采用免疫组织化学方法检测DFU、非糖尿病难治组织、创缘组织（血糖正常）中CD147、E-cadherin、N-cadherin、Slug、Phospho-RSK2等蛋白的表达情况。采用Western blotting分析高糖环境下HaCaT细胞CD147和Slug的表达情况。构建了 CD147 或 RSK2 敲低的 HaCaT 细胞。伤口愈合实验用于测试敲低 CD147 的 HaCaT 细胞的迁移能力。采用Western blotting检测敲除CD147或RSK2的HaCaT细胞中Slug的蛋白水平，探讨CD147或RSK2对EMT的影响。采用免疫沉淀（IP）法检测CD147与RSK2的相互作用。结果：边缘DFU组织上皮细胞中CD147和Slug的表达水平显着低于非糖尿病难治组织和创面边缘组织（均P
OBJECTIVES: Diabetic foot ulcer (DFU), with a high rate of amputation and mortality, is a serious complication of diabetes. However, the therapeutic effect of diabetic foot is poor. This study aimed to investigate the effect of CD147 on epithelial-mesenchymal transition (EMT) process in DFU and molecular mechanisms.METHODS: Immunohistochemistry was used to reveal the expression of several proteins, such as CD147, E-cadherin, N-cadherin, Slug, and Phospho-RSK2 in DFU, non-diabetic refractory tissues, and wound margin tissues (normal blood glucose). Western blotting was used to analyze the expression of CD147 and Slug in HaCaT cells in the high-glucose environment. HaCaT cells with CD147 or RSK2 knockdown was constructed. Wound healing assay was used to test the migration capability of HaCaT cells with knockdown of CD147. Western blotting was used to detect the protein level of Slug in HaCaT cells with CD147 or RSK2 knockdown to investigate the effects of CD147 or RSK2 on EMT. Immunoprecipitation (IP) assay was used to detect the interaction between CD147 and RSK2.RESULTS: The expression levels of CD147 and Slug in the epithelial cells of marginal DFU tissues were significantly lower than those in non-diabetic refractory tissues and wound margin tissues (all P