Nox-2 is a modulator of fibrogenesis in kidney allografts.
Nox-2 is a modulator of fibrogenesis in kidney allografts.
复制标题
DOI：
10.1111/j.1600-6143.2008.02463.x
复制
发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Reese S
中科院分区：
文献类型：
--
作者：
Djamali A;Vidyasagar A;Adulla M;Hullett D;Reese S
我们研究了经典吞噬细胞NADPH氧化酶（Nox）在肾移植肾小管间质纤维化发病机制中的作用。免疫荧光研究表明，Nox - 2和p22phox（Nox的电子传递亚基）共定位于人肾移植的肾小管间质中。在损伤区域，肾小管Nox - 2也与α - SMA共定位，提示上皮 - 间质转化（EMT）。间质巨噬细胞（CD68 +）和成纤维细胞（α - SMA +）表达Nox - 2，而移植物浸润的T细胞（CD3 +）和成熟的成纤维细胞（S100A4 +）不表达Nox - 2。这些结果在Fisher - Lewis大鼠肾移植模型中得到了证实。肾小管炎区域与Nox - 2和α - SMA相关，提示EMT。免疫印迹分析表明，在3周和6个月时，Nox - 2的上调与氧化应激（硝基酪氨酸）和纤维生成（α - SMA和磷酸化 - Smad2）相关。用Nox抑制剂（DPI或夹竹桃麻素）处理1周的同种异体移植物显示纤维连接蛋白和磷酸化 - Smad2减少，E - 钙黏蛋白水平升高。环孢素A、转化生长因子 - β1和血管紧张素II在体外（NRK52E细胞）使Nox - 2 mRNA水平增加2 - 7倍。用特异性Nox抑制剂（DPI或夹竹桃麻素）处理可防止E - 钙黏蛋白的下调和纤维连接蛋白转录本的上调。总之，这些研究表明Nox - 2通过激活转录因子Smad2、EMT和成纤维细胞参与同种异体移植物肾小管间质纤维化的发病机制。
We studied the role of classical phagocytic NADPH oxidase (Nox) in the pathogenesis of kidney allograft tubulointerstitial fibrosis. Immunofluorescence studies showed that Nox-2 and p22phox (electron transfer subunits of Nox) colocalized in the tubulointerstitium of human kidney allografts. Tubular Nox-2 also colocalized with α -SMA in areas of injury, suggestive of epithelial-to-mesenchymal transition (EMT). Interstitial macrophages (CD68+) and myofibroblasts (α -SMA+) expressed Nox-2 while graft infiltrating T cells (CD3+) and mature fibroblasts (S100A4+) were Nox-2−. These results were confirmed in the Fisher-to-Lewis rat kidney transplant model. Areas of tubulitis were associated with Nox-2 and α -SMA, suggestive of EMT. Immunoblot analyses showed that Nox-2 upregulation was associated with oxidative stress (nitrotyrosine) and fibrogenesis (α -SMA and phospho-Smad2) at 3 weeks and 6 months. Allografts treated with Nox inhibitors (DPI or apocynin) for 1 week showed reduced fibronectin and phospho-Smad2 and increased E-cadherin levels. Cyclosporine A, TGF-β1 and angiotensin II increased Nox-2 mRNA levels 2- to 7-fold in vitro (NRK52E cells). Treatment with specific Nox inhibitors (DPI or apocynin) prevented the downregulation of E-cadherin and upregulation of fibronectin transcripts. In aggregate, these studies suggest that Nox-2 is involved in the pathogenesis of allograft tubulointerstitial fibrosis via activation transcription factor Smad2, EMT and myofibroblasts.
登录
查看更多内容
影响因子：
13.6
作者：
Kondo, Shuji;Shimizu, Maki;Kagami, Shoji
通讯作者：
Kagami, Shoji
影响因子：
4.8
作者：
Gorin, Y;Block, K;Abboud, HE
通讯作者：
Abboud, HE
影响因子：
3
作者：
Göttmann, U;Oltersdorf, J;Braun, C
通讯作者：
Braun, C
影响因子：
19.6
作者：
Asaba, K;Tojo, A;Wilcox, CS
通讯作者：
Wilcox, CS
影响因子：
8.3
作者：
Modlinger, P;Chabrashvili, T;Wilcox, CS
通讯作者：
Wilcox, CS