Authors: Chen, Xionglin | Zhang, Jie | Cao, Xiaoming | Jiang, He | Wu, Zhiren | Zeng, Zi du | Jiang, Chen | Chen, Hui
Article Type:
Research Article
Abstract:
BACKGROUND: Vascular endothelial injury, a key factor in diabetic foot ulcers (DFUs) pathogenesis, is linked to the impaired proliferation and migration of vascular endothelial cells, modulated by hypoxia-inducible factor, growth factors, and inflammatory elements. OBJECTIVE: The present study assesses the role of SIKVAV (Ser-Ile-Lys-Val-Ala-Val), a peptide shown to enhance cell proliferation and migration, on mouse aortic endothelial cell (MAEC) and the corresponding molecular mechanisms. METHODS: MAEC were treated with SIKVAV at 0, 100, 200, 400, and 600 μg/mL for 0, 24, 48, and 72 h. Cell viability was tested using the CCK-8 assay. Proliferating cell nuclear
…antigen (PCNA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (Akt) levels were measured by qRT-PCR and western blot. RESULTS: SIKVAV augmented PCNA mRNA expression and stimulated vascular endothelial cell proliferation in a concentration and time-dependent fashion. Furthermore, it amplified the expression of p-ERK1/2 and p-Akt, pivotal components of the mitogen-activated protein kinase (MAPK)/ERK1/2 and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. The inhibition of these pathways suppressed PCNA mRNA expression, cell proliferation rate, and decreased p-ERK1/2 and p-Akt levels, highlighting SIKVAV’s role in promoting vascular endothelial cell proliferation via these pathways. CONCLUSION: The results of this study confirmed that SIKVAV grafted onto scaffolds can accelerate the proliferation of vascular endothelial cells for the therapy of skin wounds, and provide a theoretical basis for its application in ischemic disease as synthesized biomaterials scaffolds of tissue engineering.
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Keywords: Diabetic foot ulcers, Ser-Ile-Lys-Val-Ala-Val, vascular endothelial cell, cell proliferation, signaling pathways
DOI: 10.3233/BME-240018
Citation: Bio-Medical Materials and Engineering,
vol. Pre-press, no. Pre-press, pp. 1-12, 2024
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