Stem cell factor in a rat model of serum nephrotoxic nephritis
Stem cell factor in a rat model of serum nephrotoxic nephritis
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DOI：
10.1159/000112518
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
El Nahas, A. M.
中科院分区：
文献类型：
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作者：
El Kossi, M. M.;Haylor, J. L.;El Nahas, A. M.
背景：干细胞因子(SCF)参与了以组织重塑和纤维化为特征的多种疾病过程。在肾毒性血清性肾炎(NTN)的大鼠模型中，对生长因子(SCF)进行了评估，其特征是早期炎症，随后组织纤维化。方法：用兔抗大鼠肾小球基底膜抗体诱导雄性Wistar京都大鼠NTN。分别于第7、15、30、45天处死动物，每组4~10只。免疫组织化学染色大鼠肾脏炎症标志物ED1、CD34、SCF、c-kit、肥大细胞类胰蛋白酶和纤维化标志物、III型和IV型胶原及α-SMA。Western blotting和Northern blotting分别检测SCF蛋白和mRNA含量的变化。结果：在NTN肾组织中，肾小球、肾小管和肾间质中SCF及其受体(c-kit)的表达水平显著升高。在NTN和对照组大鼠切片中几乎未检测到肥大细胞。双重免疫染色显示SCF与α-SMA共存，SCF受体与CD34、ED1阳性细胞共存。肾小球、肾小管和肾间质中的SCF蛋白与血肌酐、蛋白尿、肾小球硬化积分和间质纤维化积分均呈直线正相关。在多变量分析中，免疫染色的肾小管干细胞因子是肾小球硬化的预测因子，免疫染色的肾小球干细胞因子预测肾小管萎缩。由于Northern印迹法检测到SCF基因表达下降，因此SCF免疫染色增强不是转录改变的结果。对NTN肾组织匀浆的免疫印迹显示SCF有两条带，43 kDa条带减少，19 kDa条带在整个研究过程中增加。结论：SCF及其受体在NTN肾重塑过程中可能起重要作用。SCF的上调可能涉及一种翻译机制，可溶性SCF蛋白KL-S1(19 KDa)是由跨膜SCF蛋白KL-S1(43kD)通过蛋白水解酶切割而来的。NTN肾脏中CD34+细胞的免疫组织化学染色为进一步评估炎症和纤维化过程中这些细胞的性质提供了依据。版权所有(C)2007 S.Karger AG，巴塞尔。
Background: Stem cell factor (SCF) has been implicated in many disease processes characterized by tissue remodelling and fibrosis. The growth factor (SCF) was evaluated in a rat model of nephrotoxic serum nephritis (NTN), characterized by early inflammation followed by later tissue fibrosis. Methods: NTN was induced in male Wistar Kyoto rats using rabbit anti-rat glomerular basement membrane antibodies. Animals were sacrificed at days 7, 15, 30 and 45 (n = 4-10 per group). Rats' kidneys were immunostained for ED1 as marker of inflammation, CD34, SCF, c-kit, mast cell tryptase and markers of fibrosis; collagens III and IV and alpha-SMA. Changes in SCF protein and mRNA content were evaluated by Western blotting and Northern blotting, respectively. Results: In the NTN kidney, levels of immunoreactive SCF and SCF receptor (c-kit) were significantly higher in glomerular, tubular and interstitial compartments. Mast cells were barely detectable in NTN and control rat sections. Double immunostaining showed the co-localization of SCF with alpha-SMA and of the SCF receptor with CD34 and ED1 positive cells. Immunostainable SCF protein in each of the 3 compartments, glomerular, tubular and interstitial, showed a positive linear correlation with serum creatinine, proteinuria, glomerulosclerosis score and interstitial fibrosis scores. Using multivariate analysis, immunostainable tubular SCF was a predictor of glomerular sclerosis and immunostainable glomerular SCF predicted tubular atrophy. Increased SCF immunostain was not a consequence of altered transcription as there was a fall in SCF mRNA determined by Northern blotting. Western blotting of NTN kidney homogenates revealed two bands for SCF, a 43-kDa band which decreased, and a 19-kDa band which increased throughout the study. Conclusion: These results highlight the potential role of SCF and its receptor in the remodelling process of the NTN kidney. Upregulation of SCF may involve a translational mechanism, with the soluble SCF protein KL-S1 (19 kDa) being derived from the transmembrane SCF protein KL-S1 (43 kD) by proteolytic cleavage. The immunohistochemical staining of few CD34+ cells in NTN kidneys warrants further evaluation of the nature of these cells in the context of the inflammatory as well as the fibrotic processes. Copyright (c) 2007 S. Karger AG, Basel.