In situ expression of connective tissue growth factor in human crescentic glomerulonephritis
In situ expression of connective tissue growth factor in human crescentic glomerulonephritis
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DOI：
10.1007/s00428-003-0959-z
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发表时间：
2004-03-01
期刊：
影响因子：
3.5
通讯作者：
Nagata, M
中科院分区：
文献类型：
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作者：
Kanemoto, K;Usui, J;Nagata, M
结缔组织生长因子(CTGF)近年来被认为是一种重要的促纤维化因子，在多种肾脏疾病伴纤维化中表达上调。本研究描述了新月体肾炎(CRGN)中CTGF mRNA的顺序定位及其与转化生长因子(TGF)-β1的关系。此外，我们通过连续切片分析检测了表达CTGF的细胞的表型。应用原位杂交和免疫组织化学方法对18例CRGN患者的肾活检标本进行检测。CTGF在正常肾小球的足细胞和壁上皮细胞(PECs)表达。此外，它在细胞新月体和纤维细胞新月体中也有很强的表达，尤其是在假管结构中。连续切片显示，新月体中大多数CTGF mRNA阳性细胞共表达上皮标记物细胞角蛋白，但不表达巨噬细胞标记物。此外，转化生长因子-β1及其受体转化生长因子-β受体-I和细胞外基质分子(I型胶原和纤维连接蛋白)与CTGF mRNA阳性的新月体共定位。我们的结果提示CTGF参与了PECs细胞外基质的产生，是促进肾小球新月体瘢痕形成过程的介质之一。
Connective tissue growth factor (CTGF) has recently been recognized as an important profibrotic factor and is up-regulated in various renal diseases with fibrosis. The present study describes the sequential localization of CTGF mRNA and its association with transforming growth factor (TGF)-beta1 in human crescentic glomerulonephritis (CRGN). Furthermore, we examined the phenotype of CTGF-expressing cells using serial section analysis. Kidney biopsy specimens from 18 CRGN patients were examined using in situ hybridization and immunohistochemistry. CTGF mRNA was expressed in the podocytes and parietal epithelial cells (PECs) in unaffected glomeruli. In addition, it was strongly expressed in the cellular and fibrocellular crescents, particularly in pseudotubule structures. Serial sections revealed that the majority of CTGF mRNA-positive cells in the crescents co-expressed the epithelial marker cytokeratin, but not a marker for macrophages. Moreover, TGF-beta1, its receptor TGF-beta receptor-I, and extracellular matrix molecules (collagen type I and fibronectin) were co-localized with CTGF mRNA-positive crescents. Our results suggest that CTGF is involved in extracellular matrix production in PECs and that it is one of the mediators promoting the scarring process in glomerular crescents.