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Nox2 Is a Mediator of Ischemia Reperfusion Injury
| Content Provider | Scilit |
|---|---|
| Author | Karim, A. S. Reese, S. R. Wilson, N. A. Jacobson, L. M. Zhong, W. Djamali, A. |
| Copyright Year | 2015 |
| Description | Journal: American Journal of Transplantation Delayed graft function (DGF) results from ischemia-reperfusion injury (IRI) and the generation of reactive oxygen species. We hypothesized that NADPH oxidase 2 (Nox2) plays an important role in pathways leading to DGF. We tested this hypothesis in vitro, in an animal model of IRI using wild type and Nox2(-/-) mice, and in patients with DGF. Under hypoxic conditions, primary tubular epithelial cells from Nox2(-/-) mice had reduced expression of MMP2, vimentin, and HSP27. BUN and creatinine levels were significantly increased in both Nox2(-/-) and WT mice at 4 weeks and 6 months after IRI, suggesting the development of acute and chronic kidney injury. At 4 weeks, kidney fibrosis (α-SMA, picrosirius) and oxidative stress (dihydroethidine, HNE) were significantly reduced in Nox2(-/-) mice, confirming the oxidative and pro-fibrotic effects of Nox2. The molecular signature of IRI using genomic analyses demonstrated a significant decline in hypoxia reponse, oxidative stress, fibrosis, and inflammation in Nox2(-/-) mice. Immunohistochemical analyses of pre-implanatation kidney allograft biopsies from patients with subsequent DGF showed significantly greater Nox2 levels and vascular injury compared with patients without DGF. These studies demonstrate that Nox2 is a modulator of IRI and its absence is associated with reduced inflammation, OS, and fibrosis. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636908/pdf |
| Ending Page | 2899 |
| Page Count | 12 |
| Starting Page | 2888 |
| e-ISSN | 16006143 |
| DOI | 10.1111/ajt.13368 |
| Journal | American Journal of Transplantation |
| Issue Number | 11 |
| Volume Number | 15 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2015-06-23 |
| Access Restriction | Open |
| Subject Keyword | Journal: American Journal of Transplantation Urology and Nephrology Animal Models: Murine Kidney (allograft) Function/dysfunction |
| Content Type | Text |
| Resource Type | Article |
