■血管内皮损伤,糖尿病足溃疡(DFU)发病机制的关键因素,与血管内皮细胞的增殖和迁移受损有关,由缺氧诱导因子调节,生长因子,和炎症元素。
■本研究评估了SIKVAV(Ser-Ile-Lys-Val-Ala-Val)的作用,一种能增强细胞增殖和迁移的肽,对小鼠主动脉内皮细胞(MAEC)的作用及相应的分子机制。
MAEC用SIKVAV以0、100、200、400和600μg/mL处理0、24、48和72小时。使用CCK-8测定法测试细胞活力。增殖细胞核抗原(PCNA),细胞外信号调节激酶1/2(ERK1/2),通过qRT-PCR和蛋白质印迹测量蛋白激酶B(Akt)水平。
■SIKVAV以浓度和时间依赖性方式增强PCNAmRNA表达并刺激血管内皮细胞增殖。此外,它扩增了p-ERK1/2和p-Akt的表达,丝裂原活化蛋白激酶(MAPK)/ERK1/2和磷脂酰肌醇-3-激酶(PI3K)/Akt信号通路的关键成分。这些途径的抑制抑制了PCNAmRNA的表达,细胞增殖率,p-ERK1/2和p-Akt水平降低,强调SIKVAV在通过这些途径促进血管内皮细胞增殖中的作用。
■这项研究的结果证实,SIKVAV移植到支架上可以加速血管内皮细胞的增殖,用于皮肤伤口的治疗,为其在缺血性疾病中作为组织工程生物材料支架的应用提供理论依据。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.