Fibroblast expression of an IκB dominant-negative transgene attenuates renal fibrosis

Tsutomu Inoue, Tsuneo Takenaka, Matsuhiko Hayashi, Toshiaki Monkawa, Jun Yoshino, Kouji Shimoda, Eric G. Neilson, Hiromichi Suzuki, Hirokazu Okada

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

It is not clear whether interstitial fibroblasts or tubular epithelial cells are primarily responsible for the profibrotic effects of NF-κB activation during renal fibrogenesis. Here, we crossed mice carrying a conditional IκB dominant-negative transgene (IκBdN) with mice transgenic for cell-specific FSP1.Cre (FSP1+ fibroblasts) or γGT.Cre (proximal tubular epithelia) and challenged all progeny with unilateral ureteral obstruction. We determined NF-κB activation by nuclear localization of phosphorylated p65 (pp65) in renal tissues after 7 days. We observed inhibition of NF-κB activation in interstitial cells and tubular epithelia in obstructed kidneys of FSP1.Cre;IκBdN and γGT.Cre;IκBdN mice, respectively, compared with IκBdN controls (P<0.05). Deposition of extracellular matrix, however, was significantly lower in the obstructed kidneys of FSP1.Cre;IκBdN mice but not in γGT.Cre;IκBdN mice (P < 0.05). In addition, levels of mRNA encoding the profibrotic PAI-1, fibronectin-EIIIA, and type I (α1) procollagen were significantly lower in obstructed kidneys of FSP1.Cre;I κBdN mice compared with γGT.Cre;IκBdN mice (P < 0.05). Taken together, these data support a profibrotic role for fibroblasts, but not proximal tubular epithelial cells, in modulating NF-κB activation during renal fibrogenesis.

Original languageEnglish
Pages (from-to)2047-2052
Number of pages6
JournalJournal of the American Society of Nephrology
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Fingerprint Dive into the research topics of 'Fibroblast expression of an IκB dominant-negative transgene attenuates renal fibrosis'. Together they form a unique fingerprint.

  • Cite this

    Inoue, T., Takenaka, T., Hayashi, M., Monkawa, T., Yoshino, J., Shimoda, K., Neilson, E. G., Suzuki, H., & Okada, H. (2010). Fibroblast expression of an IκB dominant-negative transgene attenuates renal fibrosis. Journal of the American Society of Nephrology, 21(12), 2047-2052. https://doi.org/10.1681/ASN.2010010003