Expression of connective tissue growth factor in human renal fibrosis

Expression of connective tissue growth factor in human renal fibrosis
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DOI:
10.1111/j.1523-1755.1998.00820.x
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发表时间:
1998-04-01
影响因子:
19.6
通讯作者:
Goldschmeding, R
Goldschmeding, R
中科院分区:
医学1区
文献类型:
--
作者:
Ito, Y;Aten, J;Goldschmeding, R

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慢性肾功能衰竭是一种常见的肾脏疾病,可由血液动力学、免疫学和代谢等因素引起。初始损伤可能引起不可逆的瘢痕形成,其涉及许多促炎性和纤维化细胞因子的产生,包括血小板衍生生长因子(PDGF)和转化生长因子β(TGF-β)。结缔组织生长因子(CTGF),包括cef 10、cef 61、CTGF和nov的生长调节剂家族的细胞因子,最近被描述为与硬皮病和其它瘢痕形成病症相关。我们研究了CTGF mRNA表达在65人肾活检标本的各种肾脏疾病的原位杂交。对照组肾组织CTGF mRNA主要表达于脏上皮细胞、壁上皮细胞和部分间质细胞。结缔组织生长因子在新月体肾炎、伊加肾病、局灶节段性肾小球硬化和糖尿病肾病的毛细血管外和严重系膜增生性病变中强烈上调。在慢性肾小管间质损伤的部位观察到CTGF mRNA表达的细胞数量增加,这与损伤程度相关。在肾小管间质区,大多数CTGF mRNA阳性细胞共表达α-平滑肌肌动蛋白,巨噬细胞标志物阴性。我们的研究结果表明,CTGF可能是一个共同的生长因子参与肾纤维化。
Chronic renal failure map occur in etiologically diverse renal diseases and can be caused by hemodynamic, immunologic and metabolic factors. Initial damage may evoke irreversible scarring, which involves production of a number of proinflammatory and fibrogenic cytokines, including platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Connective tissue growth factor (CTGF), a cytokine of the family of growth regulators comprising cef10, cyr61, CTGF and nov, has recently been described in association with scleroderma and other scarring conditions. We investigated CTGF mRNA expression in 65 human renal biopsy specimens of various renal diseases by in situ hybridization. In control human kidney CTGF mRNA was mainly expressed in visceral epithelial cells, parietal epithelial cells, and some interstitial cells. Connective tissue growth factor was strongly up-regulated in the extracapillary and severe mesangial proliferative lesions of crescentic glomerulonephritis, IgA nephropathy, focal and segmental glomerulosclerosis and diabetic nephropathy. An increase in the number of cells expressing CTGF mRNA was observed at sites of chronic tubulointerstitial damage, which correlated with the degree of damage. In the tubulointerstitial area the majority of the CTGF mRNA positive cells coexpressed oc-smooth muscle actin, and were negative for macrophage markers. Our results indicate that CTGF may be a common growth factor involved in renal fibrosis.