Role Of Pericytes In Regulation Of Endothelial Cell Grow

周细胞在调节内皮细胞生长中的作用已经在体外共培养系统中得到了很好的证明。在D'Amore博士小组的原始报告中，tgf - β被认为是一种潜在的介质。然而，tgf - β在人视网膜周细胞中的表达水平极低。相反，周细胞表达高水平的色素上皮衍生因子（PEDF），一种有效的抗血管生成因子。当暴露于缺氧时，周细胞中PEDF的转录和翻译水平均显著降低。重要的是，PEDF对内皮细胞的作用是剂量依赖性的。在高剂量（50 ug/ml）时，它是一种凋亡诱导剂，而在低剂量（0.5-5.0 ug/ml）时，它反而刺激内皮细胞的生长。众所周知，阻止金属蛋白酶破坏基底膜最终会阻止新血管的生长（血管生成）。周细胞也是这些金属蛋白酶抑制剂（TIMP）的主要来源。周细胞似乎通过产生PEDF和TIMP来调节内皮细胞。在糖尿病视网膜病变中，周细胞的选择性丧失是第一个形态学病变。由于周细胞在调节内皮细胞的生长中起重要作用，因此预防周细胞的早期丢失可能是防止临床明显增殖性视网膜病变进一步发展的关键。

The role of pericytes in the regulation of endothelial cell growth has been well documented with in vitro co-culture system. In the original report by the group of Dr. D'Amore, TGF-beta has been considered as a potential mediator. However, the expression levels of TGF-beta in human retinal pericytes are extremely low. Instead, pericytes express the high levels of pigment epithelium derived factor (PEDF), a potent anti-angiogenesis factor. When exposed to hypoxia, both transcription and translation levels of PEDF in pericytes are significantly decreased. Importantly, the function of PEDF to endothelial cells is dose-dependent. It acts as an apoptosis inducer at the high dose (50 ug/ml) while it rather stimulates the growth of endothelial cells at the lower doses (0.5-5.0 ug/ml). It is known that preventing the basement membrane destruction by metalloproteinases eventually prevents the new vessel growth (angiogenesis). Pericytes are also the major source of inhibitors (TIMP) of these metalloproteinases. It appears that pericytes regulate endothelial cells by producing both PEDF and TIMP. In diabetic retinopathy, the selective loss of pericytes occurs as the first morphological lesion. Since pericytes are important in regulating the growth of endothelial cells, preventing this early event of pericyte loss may be a key preventing the further progress to the clinically apparent proliferative retinopathy.