Ito Y, Aten J, Bende R J, Oemar B S, Rabelink T J, Weening J J, Goldschmeding R
Department of Pathology, University of Amsterdam, The Netherlands.
Kidney Int. 1998 Apr;53(4):853-61. doi: 10.1111/j.1523-1755.1998.00820.x.
Chronic renal failure may 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 sef10, 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 CTFG 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 alpha-smooth muscle actin, and were negative for macrophage markers. Our results indicate that CTGF may be a common growth factor involved in renal fibrosis.
慢性肾衰竭可能发生于病因多样的肾脏疾病中,可由血流动力学、免疫及代谢因素引起。初始损伤可能引发不可逆的瘢痕形成,这涉及多种促炎和促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)是由sef10、cyr61、CTGF和nov组成的生长调节因子家族中的一种细胞因子,最近已被描述与硬皮病及其他瘢痕形成情况有关。我们通过原位杂交研究了65例各种肾脏疾病的人肾活检标本中CTGF mRNA的表达。在对照人肾脏中,CTFG mRNA主要在内皮细胞、壁层上皮细胞和一些间质细胞中表达。在新月体性肾小球肾炎、IgA肾病、局灶节段性肾小球硬化和糖尿病肾病的毛细血管外及重度系膜增生性病变中,结缔组织生长因子强烈上调。在慢性肾小管间质损伤部位观察到表达CTGF mRNA的细胞数量增加,这与损伤程度相关。在肾小管间质区域,大多数CTGF mRNA阳性细胞共表达α平滑肌肌动蛋白,且巨噬细胞标志物呈阴性。我们的结果表明,CTGF可能是参与肾纤维化的一种常见生长因子。