Tumor necrosis factor-alpha regulation of insulin-like growth factor-I, type 1 IGF receptor, and IGF binding protein expression in cerebellum of transgenic mice.
Tumor necrosis factor-alpha regulation of insulin-like growth factor-I, type 1 IGF receptor, and IGF binding protein expression in cerebellum of transgenic mice.
复制标题
肿瘤坏死因子-α 对转基因小鼠小脑中胰岛素样生长因子-I、1 型 IGF 受体和 IGF 结合蛋白表达的调节。
DOI：
10.1002/jnr.10512
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
D'Ercole,AJoseph
中科院分区：
文献类型：
--
作者：
Ye,Ping;Price,Wayne;Kassiotis,George;Kollias,George;D'Ercole,AJoseph
Tumor necrosis factor‐α (TNF‐α), a proinflammatory cytokine, has been implicated in the pathogenesis of several disorders and injuries in the central nervous system (CNS). Unlike IGF‐I, which promotes CNS growth, TNF‐α causes brain growth retardation and neural damage. Recently TNF‐α has been shown to inhibit IGF‐I signaling and actions in non‐neural tissue. To investigate whether TNF‐α deleteriously influences brain growth by altering the IGF‐I system in vivo, we examined the expression of IGF‐I, the type 1 IGF receptor (IGF1R) and IGF binding proteins (IGFBPs) in the brain of transgenic (Tg) mice with murine TNF‐α overexpression. We show that overexpression of TNF‐α reduces the weights of whole brain and all brain regions examined during development. In adult TNF‐α Tg mice, cerebellum (CB) exhibited the greatest reduction in weight among the five brain regions examined, being ∼77% of that in wild‐type (WT) mice. IGF‐I abundance was decreased in the CB, as well as in cerebral cortex and diencephalon, of TNF‐α Tg mice. When compared to those in WT mice, CB IGF‐I abundance in Tg mice was reduced by ∼35%, ∼45%, and ∼40% at 2, 6, and 9 weeks of age, respectively. Of the IGFBPs studied the abundance of IGFBP‐3 and IGFBP‐4 was increased by 2–3.7‐fold, and the abundance of IGFBP‐5 was decreased by ∼3‐fold (as judged by Western immunoblot analysis). Histological analysis and immunocytochemical staining confirmed that TNF‐α specifically increases IGFBP‐3 and IGFBP‐4 immunoreactivity, as well as that of the IGF1R, in radial glial and Purkinje cells. In addition, TNF‐α alters CB cytoarchitecture, apparently by influencing granule cell migration. Our data indicate that TNF‐α alters the expression of IGF‐I system proteins in vivo, and suggest that altered expression of IGF‐I system proteins may in part explain TNF‐α deleterious actions on brain growth. © 2002 Wiley‐Liss, Inc.
