| First Author | Inoue T | Year | 2010 |
| Journal | J Am Soc Nephrol | Volume | 21 |
| Issue | 12 | Pages | 2047-52 |
| PubMed ID | 20847140 | Mgi Jnum | J:185903 |
| Mgi Id | MGI:5430478 | Doi | 10.1681/ASN.2010010003 |
| Citation | Inoue T, et al. (2010) Fibroblast expression of an IkappaB dominant-negative transgene attenuates renal fibrosis. J Am Soc Nephrol 21(12):2047-52 |
| abstractText | It is not clear whether interstitial fibroblasts or tubular epithelial cells are primarily responsible for the profibrotic effects of NF-kappaB activation during renal fibrogenesis. Here, we crossed mice carrying a conditional IkappaB dominant-negative transgene (IkappaBdN) with mice transgenic for cell-specific FSP1.Cre (FSP1(+) fibroblasts) or gammaGT.Cre (proximal tubular epithelia) and challenged all progeny with unilateral ureteral obstruction. We determined NF-kappaB activation by nuclear localization of phosphorylated p65 ((p)p65) in renal tissues after 7 days. We observed inhibition of NF-kappaB activation in interstitial cells and tubular epithelia in obstructed kidneys of FSP1.Cre;IkappaBdN and gammaGT.Cre;IkappaBdN mice, respectively, compared with IkappaBdN controls (P < 0.05). Deposition of extracellular matrix, however, was significantly lower in the obstructed kidneys of FSP1.Cre;IkappaBdN mice but not in gammaGT.Cre;IkappaBdN mice (P < 0.05). In addition, levels of mRNA encoding the profibrotic PAI-1, fibronectin-EIIIA, and type I (alpha1) procollagen were significantly lower in obstructed kidneys of FSP1.Cre;IkappaBdN mice compared with gammaGT.Cre;IkappaBdN mice (P < 0.05). Taken together, these data support a profibrotic role for fibroblasts, but not proximal tubular epithelial cells, in modulating NF-kappaB activation during renal fibrogenesis. |
