目的:为了评估肾小管上皮细胞(TEC)和间质血管内皮细胞(VEC)在人肾小球肾炎间质纤维化中的作用,我们研究了活化成纤维细胞(α-平滑肌肌动蛋白(αSMA)和波形蛋白(Vim))和转化生长因子β(TGFβ)的标志物的表达,在这些细胞的水平。
方法:我们回顾性研究了41例原发性和继发性肾小球肾炎患者的肾活检[24例男性,17名女性,平均年龄45.5±12.9岁]。使用单克隆抗体的免疫组织化学(SMA,Vim,TGFβ)使用半定量评分进行评估,这与生物学和组织学数据相关(使用评分系统量化以评估活动性炎症和慢性硬化/纤维化病变).
结果:在TECs和VECs中发现SMA和Vim作为肌成纤维细胞的标志物。TECVim表达与间质Vim表达相关(r=0.38;p=0.008),间质浸润(r=0.31;p=0.027),间质纤维化(R=0.25;p=0.042),GFR(r=-0.35;p=0.016),SMA(r=-0.42;p=0.015),TGFβ(r=0.25;p=0.046),和血红蛋白(r=-0.55;p<0.001)。VECVim表达与间质浸润(r=-0.32;p=0.023)和间质纤维化(r=-0.34;p=0.017)间接相关。
结论:我们的研究反映了VEC和主要是TEC参与纤维化的复杂性。间质标志物在肾小管细胞水平(尤其是Vim)的表达与组织学间质改变相关,随着肾功能的下降和更强烈的贫血。
OBJECTIVE: In order to assess the role played by tubular epithelial cells (TEC) and interstitial vascular endothelial cells (VEC) in interstitial fibrogenesis in human glomerulonephritis, we studied the expression of markers of activated fibroblasts (α-smooth muscle actin (αSMA) and vimentin (Vim)) and of the transforming growth factor β (TGFβ), at the level of these cells.
METHODS: We studied retrospectively 41 renal biopsies from patients with primary and secondary glomerulonephritis [24 males, 17 females, mean age 45.5 ± 12.9 years]. Immunohistochemistry using monoclonal antibodies (SMA, Vim, TGFβ) was assessed using a semiquantitative score, that was correlated with biological and histological data (quantified using a scoring system in order to assess active-inflammatory and chronic-sclerotic/fibrotic lesions).
RESULTS: The presence of SMA and Vim as markers of myofibroblasts was found in TECs and VECs. TEC Vim expression correlated with interstitial Vim expression (r = 0.38; p = 0.008), interstitial infiltrate (r = 0.31; p = 0.027), interstitial fibrosis (R = 0.25; p = 0.042), GFR (r = -0.35; p = 0.016), SMA (r = -0.42; p = 0.015), TGFβ (r = 0.25; p = 0.046), and hemoglobin (r = -0.55; p < 0.001). VEC Vim expression showed indirect correlations with interstitial infiltrate (r = -0.32; p = 0.023) and interstitial fibrosis (r = -0.34; p = 0.017).
CONCLUSIONS: Our
study reflects the complexity of the involvement of VEC and mainly of TEC in fibrosis. The expression of mesenchymal markers at the tubular cell level (especially Vim) correlates with histological interstitial changes, with the decrease of renal function and more strongly with anemia.