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Nox-2 is a modulator of fibrogenesis in kidney allografts.

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (2008-11-04)
A Djamali, A Vidyasagar, M Adulla, D Hullett, S Reese
RÉSUMÉ

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 alpha-SMA in areas of injury, suggestive of epithelial-to-mesenchymal transition (EMT). Interstitial macrophages (CD68(+)) and myofibroblasts (alpha-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 alpha-SMA, suggestive of EMT. Immunoblot analyses showed that Nox-2 upregulation was associated with oxidative stress (nitrotyrosine) and fibrogenesis (alpha-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-beta1 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.

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Sigma-Aldrich
Anticorps anti-nitrotyrosine, Chemicon®, from rabbit
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RéférenceConditionnementDisponibilitéPrixQuantité
100 μg
1 Date d'expédition estimée le 27 février 2025
463.00 CHF