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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-1
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1533-3450
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2047-52
pubmed:dateRevised
2011-1-10
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Fibroblast expression of an I?B dominant-negative transgene attenuates renal fibrosis.
pubmed:affiliation
Department of Nephrology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural