Xu Hongping, Zhang Liwei, Chen Wei, Xu Jiazhou, Zhang Ruting, Liu Ran, Zhou Lan, Hu Wenjie, Ju Rong, Lee Chunsik, Lu Weisi, Kumar Anil, Li Xuri, Tang Zhongshu
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
Oncotarget. 2017 Jul 12;8(44):76165-76173. doi: 10.18632/oncotarget.19191. eCollection 2017 Sep 29.
Caveolin-1 (Cav1) is the principle structural protein of caveolae. It plays important roles in the vascular system under both physiological and pathological conditions. Although Cav1 has been shown to inhibit microvascular permeability and has been considered as a tumor-suppressor for years, the underlying cellular mechanism has yet to be discovered. Here, we systematically investigated Cav1 functions in the main types of vascular cells, including endothelial cells (ECs), pericytes (PCs) and smooth muscle cells (SMCs). We synthesized a cell-permeable peptide called cavtratin that is derived from the Cav1 scaffolding domain. We found that cavtratin inhibited ECs in all assays, including survival, proliferation, migration and permeability assays. It also inhibited the proliferation of PCs and SMCs but had no effect on their survival or migration. The inhibitory effect of cavtratin on the proliferation of all vascular cells suggests that Cav1 plays important roles in vascular development and angiogenesis. Under physiological condition, the main function of Cav1 is to inhibit EC permeability.
小窝蛋白-1(Cav1)是小窝的主要结构蛋白。它在生理和病理条件下的血管系统中都发挥着重要作用。尽管Cav1已被证明可抑制微血管通透性,并且多年来一直被视为肿瘤抑制因子,但其潜在的细胞机制尚未被发现。在此,我们系统地研究了Cav1在主要类型血管细胞中的功能,包括内皮细胞(ECs)、周细胞(PCs)和平滑肌细胞(SMCs)。我们合成了一种源自Cav1支架结构域的可穿透细胞的肽,称为小窝抑制素。我们发现小窝抑制素在所有实验中均抑制内皮细胞,包括存活、增殖、迁移和通透性实验。它还抑制周细胞和平滑肌细胞的增殖,但对它们的存活或迁移没有影响。小窝抑制素对所有血管细胞增殖的抑制作用表明,Cav1在血管发育和血管生成中起重要作用。在生理条件下,Cav1的主要功能是抑制内皮细胞通透性。