细胞周期蛋白依赖激酶2
血管平滑肌
生物
细胞生长
细胞生物学
心肌细胞
形态学(生物学)
细胞周期
周期素
细胞周期蛋白
细胞
激酶
遗传学
内分泌学
蛋白激酶A
平滑肌
动物
作者
Zhecun Wang,Yunling Qi,Rui Wang,Weibin Wu,Zilun Li,Sheng Wang,Ruiming Liu,Chunxiang Zhang,Wen Li,Shenming Wang
摘要
Despite the high prevalence of varicose veins, the underlying pathogenesis of this disease remains unclear. The present study aims to explore the role of insulin-like growth factor binding protein 6 (IGFBP6) in vascular smooth muscle cells (VSMCs). Using a protein array approach, we identified several differentially expressed proteins between varicose great saphenous veins and normal great saphenous veins. Bioinformatic analysis showed that IGFBP6 was closely related to cell proliferation. Further validation confirmed that IGFBP6 was one of the most highly expressed proteins in varicose vein tissue. Knocking down IGFBP6 in VSMCs significantly attenuated cell proliferation and induced the S phase arrest during the cell cycle. Further experiments demonstrated that IGFBP6 knockdown increased cyclin E ubiquitination, which reduced expression of cyclin E and phosphorylation of CDK2. Furthermore, IGFBP6 knockdown arrested centrosome replication, which subsequently influenced VSMC morphology. Ultimately, IGFBP6 was validated to be involved in VSMC proliferation in varicose vein tissues. The present study reveals that IGFBP6 is closely correlated with VSMC biological function and provides unprecedented insights into the underlying pathogenesis of varicose veins.
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