Insulin-like growth factor binding proteins modulate Muller cell responses to insulin-like growth factors.
Insulin-like growth factor binding proteins modulate Muller cell responses to insulin-like growth factors.
复制标题
胰岛素样生长因子结合蛋白调节米勒细胞对胰岛素样生长因子的反应。
DOI：
10.1167/iovs.04-0054
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发表时间：
2004
影响因子：
4.4
通讯作者：
Guidry,Clyde
中科院分区：
文献类型：
--
作者：
King,JefferyL;Guidry,Clyde
目的。在糖尿病纤维性收缩的眼部组织中一致发现了m<s:1> ller细胞，并在胰岛素样生长因子I的作用下产生导致视网膜脱离的牵引力。最近的研究表明，糖尿病相关的玻璃体胰岛素样生长因子活性的增加不能仅仅归因于浓度的增加，这表明玻璃体生长因子控制机制中涉及更复杂的生化变化。本研究的目的是评估玻璃体胰岛素样生长因子结合蛋白（igfbp）在控制生长因子活性方面的作用。在组织培养实验中，评估了天然和重组igfbp对igf - i和igf - ii刺激的<s:1> ller细胞的影响，该实验包括在三维胶原凝胶上培养细胞并监测进行性基质凝结。Western配体印迹法评估了<s:1> ller细胞分泌的蛋白酶对IGFBP的降解作用，并通过单独培养IGFBP来评估其直接刺激作用。IGFBP对m<s:1> ller细胞的直接刺激作用是显著的，但相对温和，并且未检测到IGFBP通过m<s:1> ller细胞分泌的蛋白酶进行调节。相反，IGFBP对IGF-I和igf - ii的抑制作用是高度可变的，在某些情况下是深刻的。IGFBP-3有效抑制IGF-I和igf - ii的刺激，其浓度与生长因子相当。IGFBP-1、-2、-4和5作为抑制剂的有效性为中等，活性比IGFBP-3低3- 11倍。IGFBP-6对igf - 1几乎没有抑制作用，但对igf - 2有中等抑制作用。IGFBP对igf - i和igf - ii刺激的<s:1>勒细胞的作用主要是抑制性的，只有有限的生理相关性的适度直接刺激作用。IGFBP-2和igfbp -3是玻璃体中发现的主要结合蛋白，很可能是玻璃体生长因子汇，通过隔离控制配体活性。
purpose. Müller cells are consistently identified in diabetic fibrocontractive ocular tissues and, in response to insulin-like growth factor I, generate tractional forces of the type that cause retinal detachment. Recent studies suggest that diabetes-associated increases in vitreous insulin-like growth factor activity cannot be attributed to simple increases in concentration alone, suggesting that more complex biochemical changes in vitreous growth factor control mechanisms are involved. The goal of this study was to evaluate the contributions of vitreous insulin-like growth factor–binding proteins (IGFBPs) toward control of growth factor activity.methods. Native and recombinant IGFBPs effects were evaluated on IGF-I–and-II–stimulated Müller cells in tissue culture assays that involved cell incubation on three-dimensional collagen gels and that monitored progressive matrix condensation. IGFBP degradation by Müller cell–secreted proteases was assessed in Western ligand blots, and direct stimulatory effects were evaluated by incubating cells with IGFBPs alone.results. IGFBP direct stimulatory effects on Müller cells were significant, but relatively modest, and IGFBP modulation through Müller cell–secreted proteases was undetectable. In contrast, IGFBP inhibitory effects on IGF-I and-II were highly variable and, in some cases, profound. IGFBP-3 effectively inhibited IGF-I and-II stimulation with detectable effects at concentrations equimolar to the growth factor. IGFBP-1,-2,-4, and-5 were of intermediate effectiveness as inhibitors, 3-to 11-fold less active than IGFBP-3. IGFBP-6 had virtually no inhibitory effects on IGF-I, but was moderately effective against IGF-II.conclusions. IGFBP effects on IGF-I–and-II–stimulated Müller cells are primarily inhibitory with only modest direct stimulatory effects of limited physiologic relevance. IGFBP-2 and-3, the major binding proteins identified in vitreous, most likely function as the vitreous growth factor sink and control ligand activity through sequestration.