Expression and localization of insulin-like growth factor binding proteins in normal and proteinuric kidney glomeruli
Expression and localization of insulin-like growth factor binding proteins in normal and proteinuric kidney glomeruli
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DOI：
10.1111/j.1440-1797.2010.01285.x
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发表时间：
2010-10-01
期刊：
影响因子：
2.5
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
--
作者：
Fujinaka, Hidehiko;Katsuyama, Koichi;Yamamoto, Tadashi
目的：胰岛素样生长因子I（IGF-I）通过IGF-I受体（IGF-IR）以内分泌和/或局部方式作用于靶细胞，其作用受多种IGF结合蛋白（IGFBP）调节。为了阐明IGFBP在肾小球中的作用，检测其基因的表达和定位，并与正常肾小球和蛋白尿肾小球进行比较。方法：利用人肾小球和皮质构建cDNA微阵列数据库（MAd-761）。采用聚合酶链反应（PCR）和原位杂交（ISH）技术检测大鼠肾小球和皮质中IGF-I、IGF-1 R和IGFBP（1-10）的基因表达水平，并比较IGFBP在正常和蛋白尿大鼠肾小球中的表达水平。在PCR中，显示肾小球中IGFBP-2、-7、-8和-10基因的表达水平与其在皮质中的水平相比增加了一倍以上。在ISH中，发现IGFBP-2、-7、-8和-10基因定位于肾小球细胞（包括足细胞）中，并且在炎症性肾小球中观察到其表达增加。IGF-I基因表达定位于肾小球足细胞，而IGF-IR基因表达于肾小球足细胞和皮质小管细胞。结论：IGFBP-2、-7、-8和-10由正常和损伤的肾小球足细胞产生，并可能调节肾脏足细胞和/或皮质小管细胞局部IGF-I的作用。
Aim:Insulin-like growth factor I (IGF-I) acts on target cells in an endocrine and/or local manner through the IGF-I receptor (IGF-IR), and its actions are modulated by multiple IGF binding proteins (IGFBP). To elucidate the roles of local IGFBP in kidney glomeruli, the expression and localization of their genes were examined and compared with normal and proteinuric kidney glomeruli.Methods:A cDNA microarray database (MAd-761) was constructed using human kidney glomeruli and cortices. The gene expression levels of IGF-I, IGF-1R and IGFBP (1-10) were examined in glomeruli and cortices by polymerase chain reaction (PCR) and in situ hybridization (ISH), and the expression levels of IGFBP that were abundantly found in the glomerulus were compared between normal and proteinuric kidneys in rats and humans.Results:IGFBP-2, -7 and -8 were demonstrated to be abundantly and preferentially expressed in the glomerulus. In PCR, the expression levels of the IGFBP-2, -7, -8 and -10 genes in glomeruli were shown to have more than doubled compared with their levels in the cortices. In ISH, the IGFBP-2, -7, -8 and -10 genes were found to be localized in glomerular cells including podocytes, and their increased expression was observed in inflammatory glomeruli. IGF-I gene expression was localized in glomerular podocytes, whereas the IGF-IR gene was expressed in glomerular podocytes and cortical tubular cells. In nephrotic rats, the expression of the IGFBP-10 gene was increased in glomerular podocytes; however, the expression levels of IGFBP-2, -7 and -8 did not change.Conclusion:IGFBP-2, -7, -8 and -10 are produced by normal and injured glomerular podocytes and may regulate local IGF-I actions in podocytes and/or cortical tubular cells in the kidney.