Connective tissue growth factor participates in scar formation of crescentic glomerulonephritis
Connective tissue growth factor participates in scar formation of crescentic glomerulonephritis
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DOI：
10.1097/01.lab.0000096711.58115.46
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发表时间：
2003-11-01
影响因子：
5
通讯作者：
Nagata, M
中科院分区：
文献类型：
--
作者：
Kanemoto, K;Usui, J;Nagata, M
肾小球新月体是各种肾脏疾病进展的主要决定因素。已知某些类型的生长因子参与新月体的进化和随后的疤痕形成。尽管肾小球壁上皮细胞（PEC）是细胞新月体的主要成分，但生长因子对PEC的影响尚不清楚。我们进行了免疫组织化学研究和原位杂交，以检查结缔组织生长因子 (CTGF) 表达的变化，并鉴定 Wistar 京都大鼠新月体肾小球肾炎模型中新月体中的 CTGF 合成细胞。此外，我们还研究了成纤维细胞生长因子（FGF）-2、血小板源性生长因子（PDGF）-BB、转化生长因子（TGF）-β和CTGF在已建立的大鼠PEC细胞系（PEC系）中细胞增殖和基质合成中的作用。在大鼠新月体肾小球肾炎的急性期，新月体的主要成分是巨噬细胞，其不表达CTGF mRNA。然而，在晚期阶段，新月体强烈表达CTGF mRNA和上皮标记物泛钙粘蛋白，但不表达巨噬细胞标记物ED1，这表明PECs合成了CTGF。在 PEC 系中，与 PDGF-BB 相比，FGF-2 主要促进 [H-3] 胸苷掺入。 TGF-β 和 PDGF-BB 均强烈刺激细胞外基质合成，并与内源性 CTGF 上调相关，但 TGF-β 表现出主导作用。 FGF-2对其影响较小。此外，使用反义寡脱氧核苷酸阻断内源性 CTGF 显着减弱 TGF-β 和 PDGF-BB 诱导的细胞外基质合成。这些结果表明，多种生长因子促进 PEC 中的细胞增殖和基质产生。 CTGF 介导的 PEC 中通过 TGF-β 或 PDGF-BB 途径产生的基质可能在一定程度上在新月体疤痕形成的过程中发挥作用。
Glomerular crescents area major determinant of progression in various renal diseases. Some types of growth factors are known to be involved in the evolution of crescents and the subsequent scar formation. Although glomerular parietal epithelial cells (PECs) are the major component of cellular crescents, the influence of growth factors on PECs is unknown. We performed immunohistochemical studies and in situ hybridization to examine alterations in connective tissue growth factor (CTGF) expression and to identify CTGF-synthesizing cells in crescents in the crescentic glomerulonephritis model of Wistar Kyoto rats. In addition, we examined the roles of fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-beta, and CTGF in cell proliferation and matrix synthesis in an established rat PEC cell line (PEC line). In an acute phase of rat crescentic glomerulonephritis, a major component of the crescents were macrophages, which did not express CTGF mRNA. However, in the advanced phase, crescents strongly expressed CTGF mRNA and the epithelial marker pan-cadherin but did not express the macrophage marker ED1, suggesting that PECs synthesized the CTGF. In the PEC line, FGF-2 predominantly promoted [H-3]thymidine incorporation compared with PDGF-BB. Both TGF-beta and PDGF-BB strongly stimulated extracellular matrix synthesis in association with up-regulation of endogenous CTGF, but TGF-beta showed a predominant role. FGF-2 had a minor effect on it. In addition, blockade of endogenous CTGF using an antisense oligodeoxynucleotide significantly attenuated both TGF-beta- and PDGF-BB-induced extracellular matrix synthesis. These results suggest that several growth factors promote cell proliferation and matrix production in PECs. CTGF-mediated matrix production via the TGF-beta or PDGF-BB pathway in PECs may, in part, play a role in the progression of scar formation in crescents.