Vitreous IGFBP-3 Effects on Muller Cell Proliferation and Tractional Force Generation
Vitreous IGFBP-3 Effects on Muller Cell Proliferation and Tractional Force Generation
复制标题
DOI：
10.1167/iovs.11-8683
复制
发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Guidry, Clyde
中科院分区：
文献类型：
--
作者：
King, Jeffery L.;Guidry, Clyde
目的.本实验室以前的研究表明，玻璃体胰岛素样生长因子结合蛋白-3（IGFBP-3）是完整蛋白的生物活性片段。本研究的目的是表征其对Muller细胞增殖和牵引力产生的影响，这些活动与增殖性糖尿病视网膜病变（PDR）有关。从正常猪视网膜分离Muller细胞。从正常人血浆中分离玻璃体型IGFBP-3片段，并与完整重组蛋白在组织培养模型中调节Muller细胞增殖和牵引力产生的能力进行比较。血清和血小板源性生长因子（PDGF）刺激Muller细胞增殖，但胰岛素样生长因子（IGF）-I或IGF-II不刺激。细胞对单独的IGFBP-3或IGFBP-3片段或与IGF-I或IGF-II的组合类似地无应答。相反，Muller细胞表现出对IGF-I、IGF-II和PDGF的强烈细胞外基质收缩。完整的IGFBP-3减弱细胞外基质对IGF-I和IGF-II的收缩反应，而IGFBP-3片段仅调节细胞对IGF-II的反应。两种结合蛋白均不改变细胞对PDGF的反应。完整的IGFBP-3调节由IGF-I和IGF-II刺激的Muller细胞牵引力产生，而玻璃体型片段的作用仅限于IGF-II。猪Muller细胞增殖对PDGF有反应，但对IGF-I或IGF-II无反应。两种形式的IGFBP-3单独或与IGF组合也没有促有丝分裂作用。似乎PDR中的Muller细胞牵引力的产生是由玻璃体IGF活性驱动的，并且增殖是由IGF系统外的生长因子刺激的。（Invest Ophthalmol维斯科学。2012;53：93-99）DOI：10.1167/iovs.11-8683
PURPOSE. Previous studies from this laboratory revealed that vitreous insulin-like growth factor binding protein-3 (IGFBP-3) is a biologically active fragment of the intact protein. The goal of this study was to characterize its effects on Muller cell proliferation and tractional force generation, activities relevant to proliferative diabetic retinopathy (PDR).METHODS. Muller cells were isolated from normal porcine retina. The vitreous-type IGFBP-3 fragment was isolated from normal human plasma and compared with intact recombinant protein for the ability to modulate Muller cell proliferation and tractional force generation in tissue culture models.RESULTS. Muller cells were stimulated to proliferate by serum and platelet-derived growth factor (PDGF), but not insulin-like growth factor (IGF)-I or IGF-II. The cells were similarly unresponsive to IGFBP-3 or the IGFBP-3 fragment alone or in combination with IGF-I or IGF-II. In contrast, Muller cells demonstrated robust extracellular matrix contraction in response to IGF-I, IGF-II, and PDGF. Intact IGFBP-3 attenuated extracellular matrix contraction in response to IGF-I and IGF-II while the IGFBP-3 fragment modulated cell responses to IGF-II only. Neither binding protein altered cell responses to PDGF.CONCLUSIONS. Intact IGFBP-3 modulates Muller cell tractional force generation stimulated by IGF-I and IGF-II while the effects of the vitreous-type fragment are limited to IGF-II. Porcine Muller cells proliferate in response to PDGF, but not IGF-I or IGF-II. Both forms of IGFBP-3 are also without mitogenic effects alone or in combination with IGFs. It appears that Muller cell tractional force generation in PDR is driven by vitreous IGF activity and proliferation is stimulated by growth factors outside of the IGF system. (Invest Ophthalmol Vis Sci. 2012;53:93-99) DOI:10.1167/iovs.11-8683