SIKVAV promotion proliferation of vascular endothelial cells and related mechanisms

Article type: Research Article

Authors: Chen, Xionglin^a; | Zhang, Jie^a | Cao, Xiaoming^b | Jiang, He^a | Wu, Zhiren^c | Zeng, Zi du^c | Jiang, Chen^d | Chen, Hui^b

Affiliations: [a] Department of Histology, Embryology and Medical Genetics, Jiangxi Provincial Key Laboratory of Cell Precision Therapy, School of Basic Medical Sciences, Jiujiang University, Jiujiang, China | [b] Department of Anatomy, School of Basic Medical Sciences, Jiujiang University, Jiujiang, China | [c] Department of Preventive Medicine, School of Basic Medical Sciences, Jiujiang University, Jiujiang, China | [d] Department of Oral medicine, School School of Basic Medical Sciences, Jiujiang University, Jiujiang, China

Correspondence: [*] Corresponding author: Dr. Xionglin Chen, Department of Histology, Embryology and Medical Genetics, School of Medicine, Jiujiang University, Jiujiang 332000, China. Tel.: +8607928570078; Fax: +8607928570078; E-mail: [email protected]

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.

Keywords: Diabetic foot ulcers, Ser-Ile-Lys-Val-Ala-Val, vascular endothelial cell, cell proliferation, signaling pathways

DOI: 10.3233/BME-240018

Journal: Bio-Medical Materials and Engineering, vol. Pre-press, no. Pre-press, pp. 1-12, 2024