AJP - Renal Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 296: F328-F336, 2009. First published November 26, 2008; doi:10.1152/ajprenal.00484.2007
0363-6127/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
296/2/F328    most recent
00484.2007v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kono, K.
Right arrow Articles by Aoyama, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kono, K.
Right arrow Articles by Aoyama, T.

PPAR{alpha} attenuates the proinflammatory response in activated mesangial cells

Keiichi Kono,1,2 Yuji Kamijo,1,2 Kazuhiko Hora,2 Kyoko Takahashi,1,2 Makoto Higuchi,2 Kendo Kiyosawa,2 Hidekazu Shigematsu,3 Frank J. Gonzalez,4 and Toshifumi Aoyama1

1Department of Metabolic Regulation, Institute on Aging and Adaptation, 2Department of Internal Medicine, and 3Department of Pathology, Shinshu University School of Medicine, Matsumoto, Japan; and 4Laboratory of Metabolism, National Cancer Institute, Bethesda, Maryland

Submitted 16 October 2007 ; accepted in final form 20 November 2008

The activated mesangial cell is an important therapeutic target for the control of glomerulonephritis. The peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) has attracted considerable attention for its anti-inflammatory effects; however, its roles in the mesangial cells remain unknown. To determine the anti-inflammatory function of PPAR{alpha} in mesangial cells, wild-type and Ppara-null cultured mesangial cells were exposed to lipopolysaccharide (LPS). LPS treatment caused enhanced proinflammatory responses in the Ppara-null cells compared with wild-type cells, as revealed by the induction of interleukin-6, enhanced cell proliferation, and the activation of the nuclear factor (NF)-{kappa}B signaling pathway. In wild-type cells resistant to inflammation, constitutive expression of PPAR{alpha} was undetectable. However, LPS treatment induced the significant appearance and substantial activation of PPAR{alpha}, which would attenuate the proinflammatory responses through its antagonizing effects on the NF-{kappa}B signaling pathway. The induction of PPAR{alpha} was coincident with the appearance of {alpha}-smooth muscle actin, which might be associated with the phenotypic changes of mesangial cells. Moreover, another examination using LPS-injected wild-type mice demonstrated the appearance of PPAR{alpha}-positive cells in glomeruli, suggesting in vivo correlation with PPAR{alpha} induction. These results suggest that PPAR{alpha} plays crucial roles in the attenuation of inflammatory response in activated mesangial cells. PPAR{alpha} might be a novel therapeutic target against glomerular diseases.

inflammatory response; lipopolysaccharide; nuclear factor-{kappa}B; phenotypic changes; peroxisome proliferator-activated receptor {alpha}


Address for reprint requests and other correspondence: Y. Kamijo, Dept. of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu Univ. School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan (e-mail: yujibeat{at}shinshu-u.ac.jp)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.