Wang Kui, Ge Yongmei, Yang Yongshuai, Li Zhenjian, Liu Jiayi, Xue Yizebang, Zhang Yuanjun, Pang Xiangchao, Ngan A H W, Tang Bin
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Department of Mechanical Engineering, University of Hong Kong, Hong Kong 999077, China.
Regen Biomater. 2024 Jan 25;11:rbae004. doi: 10.1093/rb/rbae004. eCollection 2024.
Diabetes is one of the most prevalent diseases worldwide. The tissue regeneration of diabetes patients is known to be rather tricky as the result of vascular dysfunction, and this leads to various clinical complications including diabetic foot ulcers. The vascular endothelial cells, which compactly line the inner surface of blood vessels, are responsible for the growth and maintenance of blood vessels and play an essential role in tissue regeneration. Although the mechanical properties of cells are generally known to be regulated by physiological/pathological conditions, few studies have been performed to investigate vascular endothelial cellular mechanics under hyperglycemia and the biological functions related to tissue regeneration. In this study, we conduct a systematic investigation of this issue. The results suggested that the stiffness of human umbilical vein endothelial cells (HUVECs) can be significantly regulated by the glucose concentration, subsequently, leading to significant alterations in cell migration and proliferation capabilities that are closely related to tissue regeneration. The rearrangement of the cytoskeleton induced by hyperglycemia through Cdc42 was found to be one of the pathways for the alteration of the cell stiffness and the subsequent cell dysfunctions. Therefore, we suggested that the inhibition of Cdc42 might be a promising strategy to facilitate various tissue regeneration for diabetes patients.
糖尿病是全球最普遍的疾病之一。由于血管功能障碍,糖尿病患者的组织再生相当棘手,这会导致包括糖尿病足溃疡在内的各种临床并发症。紧密排列在血管内表面的血管内皮细胞负责血管的生长和维持,在组织再生中起着至关重要的作用。虽然一般认为细胞的力学特性受生理/病理条件调节,但很少有研究调查高血糖状态下血管内皮细胞力学以及与组织再生相关的生物学功能。在本研究中,我们对这个问题进行了系统调查。结果表明,葡萄糖浓度可显著调节人脐静脉内皮细胞(HUVECs)的硬度,随后导致与组织再生密切相关的细胞迁移和增殖能力发生显著改变。发现高血糖通过Cdc42诱导的细胞骨架重排是细胞硬度改变及随后细胞功能障碍的途径之一。因此,我们认为抑制Cdc42可能是促进糖尿病患者各种组织再生的一种有前景的策略。