Morrison Margaret E, Palenski Tammy L, Jamali Nasim, Sheibani Nader, Sorenson Christine M
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, H4/444 CSC, Madison, WI 53792-4108, USA.
Int J Cell Biol. 2013;2013:297537. doi: 10.1155/2013/297537. Epub 2013 Oct 31.
Apoptosis of vascular cells, including pericytes and endothelial cells, contributes to disease pathogenesis in which vascular rarefaction plays a central role. Bim is a proapoptotic protein that modulates not only apoptosis but also cellular functions such as migration and extracellular matrix (ECM) protein expression. Endothelial cells and pericytes each make a unique contribution to vascular formation and function although the details require further delineation. Here we set out to determine the cell autonomous impact of Bim expression on retinal endothelial cell and pericyte function using cells prepared from Bim deficient (Bim(-/-)) mice. Bim(-/-) endothelial cells displayed an increased production of ECM proteins, proliferation, migration, adhesion, and VEGF expression but, a decreased eNOS expression and nitric oxide production. In contrast, pericyte proliferation decreased in the absence of Bim while migration, adhesion, and VEGF expression were increased. In addition, we demonstrated that the coculturing of either wild-type or Bim(-/-) endothelial cells with Bim(-/-) pericytes diminished their capillary morphogenesis. Thus, our data further emphasizes the importance of vascular cell autonomous regulatory mechanisms in modulation of vascular function.
包括周细胞和内皮细胞在内的血管细胞凋亡，在以血管稀疏为核心作用的疾病发病机制中发挥作用。Bim是一种促凋亡蛋白，不仅调节细胞凋亡，还调节细胞功能，如迁移和细胞外基质（ECM）蛋白表达。尽管具体细节尚需进一步阐明，但内皮细胞和周细胞对血管形成和功能均有独特贡献。在此，我们利用从Bim基因缺陷（Bim(-/-)）小鼠制备的细胞，来确定Bim表达对视网膜内皮细胞和周细胞功能的细胞自主影响。Bim(-/-)内皮细胞表现出ECM蛋白产生增加、增殖、迁移、黏附以及VEGF表达增加，但eNOS表达和一氧化氮产生减少。相反，在缺乏Bim的情况下，周细胞增殖减少，而迁移、黏附以及VEGF表达增加。此外，我们证明，野生型或Bim(-/-)内皮细胞与Bim(-/-)周细胞共培养会削弱它们的毛细血管形态发生。因此，我们的数据进一步强调了血管细胞自主调节机制在调节血管功能中的重要性。
