| First Author | Das S | Year | 2012 |
| Journal | Physiol Genomics | Volume | 44 |
| Issue | 7 | Pages | 430-42 |
| PubMed ID | 22318993 | Mgi Jnum | J:220427 |
| Mgi Id | MGI:5634644 | Doi | 10.1152/physiolgenomics.00147.2011 |
| Citation | Das S, et al. (2012) Activation of IKK/NF-kappaB provokes renal inflammatory responses in guanylyl cyclase/natriuretic peptide receptor-A gene-knockout mice. Physiol Genomics 44(7):430-42 |
| abstractText | The present study was aimed at determining the consequences of the disruption of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) on proinflammatory responses of nuclear factor kappa B, inhibitory kappa B kinase, and inhibitory kappa B alpha (NF-kappaB, IKK, IkappaBalpha) in the kidneys of mutant mice. The results showed that the disruption of Npr1 enhanced the renal NF-kappaB binding activity by 3.8-fold in 0-copy (-/-) mice compared with 2-copy (+/+) mice. In parallel, IKK activity and IkappaBalpha protein phosphorylation were increased by 8- and 11-fold, respectively, in the kidneys of 0-copy mice compared with wild-type mice. Interestingly, IkappaBalpha was reduced by 80% and the expression of proinflammatory cytokines and renal fibrosis were significantly enhanced in 0-copy mice than 2-copy mice. Treatment of 0-copy mice with NF-kappaB inhibitors andrographolide, pyrrolidine dithiocarbamate, and etanercept showed a substantial reduction in renal fibrosis, attenuation of proinflammatory cytokines gene expression, and significantly reduced IKK activity and IkBalpha phosphorylation. These findings indicate that the systemic disruption of Npr1 activates the renal NF-kappaB pathways in 0-copy mice, which transactivates the expression of various proinflammatory cytokines to initiate renal remodeling; however, inhibition of NF-kappaB pathway repairs the abnormal renal pathology in mutant mice. |
