| pubmed-article:20847140 | pubmed:abstractText | It is not clear whether interstitial fibroblasts or tubular epithelial cells are primarily responsible for the profibrotic effects of NF-?B activation during renal fibrogenesis. Here, we crossed mice carrying a conditional I?B dominant-negative transgene (I?BdN) with mice transgenic for cell-specific FSP1.Cre (FSP1(+) fibroblasts) or ?GT.Cre (proximal tubular epithelia) and challenged all progeny with unilateral ureteral obstruction. We determined NF-?B activation by nuclear localization of phosphorylated p65 ((p)p65) in renal tissues after 7 days. We observed inhibition of NF-?B activation in interstitial cells and tubular epithelia in obstructed kidneys of FSP1.Cre;I?BdN and ?GT.Cre;I?BdN mice, respectively, compared with I?BdN controls (P < 0.05). Deposition of extracellular matrix, however, was significantly lower in the obstructed kidneys of FSP1.Cre;I?BdN mice but not in ?GT.Cre;I?BdN mice (P < 0.05). In addition, levels of mRNA encoding the profibrotic PAI-1, fibronectin-EIIIA, and type I (?1) procollagen were significantly lower in obstructed kidneys of FSP1.Cre;I?BdN mice compared with ?GT.Cre;I?BdN mice (P < 0.05). Taken together, these data support a profibrotic role for fibroblasts, but not proximal tubular epithelial cells, in modulating NF-?B activation during renal fibrogenesis. | lld:pubmed |
