结缔组织生长因子在肾间质纤维化中的表达及其意义

Association of renal connective tissue growth factor expression with tubulointerstitial fibrosis in patients with primary glomerulonephritis

目的 :研究结缔组织生长因子 (connectivetissuegrowthfactor,CTGF)在原发性肾小球肾炎小管间质病变中的表达及其与肾间质纤维化之间的关系。 方法 :选择不同类型原发性肾小球肾炎患者 42例 ,根据小管间质病变分级分为四组 :0级 8例 ,1级 12例 ,2级 12例 ,3级 10例。应用免疫组织化学方法分别观察四组中CTGF、TGF β1、FN和COL Ⅲ的表达 ,并将CTGF表达水平与患者血肌酐 (SCr)和内生肌酐清除率 (Ccr)进行比较。 结果 :肾小管上皮细胞 (从近端小管到髓质集合管 )是间质中CTGF的主要来源 ,CTGF表达量与肾小管间质病变程度成正比 (P=0 0 0 5 )。此外 ,CTGF与TGF β1、FN和COL Ⅲ的表达量成正相关 (P均 <0 0 5 ) ;与患者Ccr升高水平成正比 (P <0 0 0 5 )。 结论 :随着慢性肾小管间质病变程度加重 ,CTGF蛋白质分子表达量显著增加 ,它可能在肾间质纤维化形成过程中起重要作用。CTGF作为TGF β1的下游因子 ,可能通过促进细胞外基质 (ECM)如FN和COL Ⅲ等合成增加 ,参与肾间质纤维化发生。

Objective:Connective tissue growth factor(CTGF)is a fibrogenic cytokine which plays a key role in the maintenance of persistent fibrosis.This study aimed at the association of renal expression of CTGF with tubulointerstitial fibrosis in patients with primary glomerulonephritis. Methodology:Renal expression of CTGF,transforming growth factor-β1(TGF-β1),fibronectin(FN)and collagen Ⅲ(COL-Ⅲ)were investigated with immunohistochemistry assays in 42 patients with primary glomerulonephritis,including 16 with IgA nephropathy,10 with FSGS,4 with MN,8 with minor lesion and 4 with MCD.The tubulointerstitial injuries was graded into four degree groups according to the extent of cortical interstitial fibrosis,with 8 patients in Grade Ⅰ group,12 in Grade Ⅱ group,12 in Grade Ⅲ group,10 in Grade Ⅳ group. Results:CTGF was detected in tubular epithelial cells in all the renal biopsy specimens.Intensive expression of CTGF was observed in tubulointerstitial area with severe lesion,with the most prominent in the tubular epithelial cells,next the interstitial fibroblasts,while no detectable expression of CTGF in the glomeruli.The expression intensity of CTGF was found correlated to the grade of tubulointerstitial damage(P=0.005),as well asthose of TGF-β1(P<0.05),FN(P<0.001)and COL-Ⅲ(P<0.05).Markedly expressed TGF-β1 was detected in both glomerular and tubulointerstitial area,including epithelial cells,fibroblasts and inflammatory cells.The expression of CTGF in tubulointerstitial injury area was found correlated with those of TGF-β1(P<0.05),FN(P<0.01)and COL-Ⅲ(P<0.05). Conclusion:Our results indicate that CTGF,as a downstream factor of TGF-β1,may be induced by TGF-β1 and mediate some of the pro-fibrotic actions of TGF-β1 such as increasing the synthesis and accumulation of extracellular matrix in tubulointerstitial area.The present study demonstrated that increased tubulointerstitial expression of CTGF may play a role in the development and progression of tubulointerstitial fibrosis in patients with primary glomerulonepritis.