NDT Advance Access originally published online on January 25, 2007
Nephrology Dialysis Transplantation 2007 22(4):1041-1051; doi:10.1093/ndt/gfl766
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hypoxia reduces the expression and anti-inflammatory effects of peroxisome proliferator-activated receptor-
in human proximal renal tubular cells
1Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 2Department of Anesthesia, School of Medicine, Kyoto University, Kyoto, Japan and 3Department of Biochemistry, School of Medicine, Niigata University
Correspondence and offprint requests to: Hideki Kimura, Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, 23 Matsuokashimoaizuki, Eiheiji-cho, Yoshida, Fukui 910-1193, Japan. Email: hkimura{at}fmsrsa.fukui-med.ac.jp
 |
Abstract |
|---|
Background. Peroxisome proliferator-activated receptor (PPAR)-
may counteract tissue fibrosis via its anti-inflammatory actions, while hypoxia, a new pro-fibrotic factor, reportedly modifies PPAR- expression. However, the effects of hypoxia on the expression and anti-inflammatory actions of PPAR- have yet remained to be clarified in renal tubular cells.
Methods. Confluent human proximal renal tubular epithelial cells (HPTECs) were exposed to hypoxia (1% O2) and/or TNF-
at 10 ng/ml for up to 48 h. The cells were incubated with PPAR- agonists, 15d-PGJ2 or pioglitazone, for 30 min before stimulation. Precise amounts of PPAR- and MCP-1 mRNA and protein were measured by TaqMan quantitative PCR and immunoblot or ELISA, respectively.
Results. A cDNA array analysis identified PPAR- as one of the hypoxia-affected genes in HPTECs. Hypoxia reduced mRNA levels of PPAR- at 24 and 48 h and protein levels at 6 and 48 h. Knockout of hypoxia-inducible factor-1 (HIF-1) with its dominant negative form did not block the hypoxia-induced reduction in PPAR- expression. PPAR-'s activation with 15d-PGJ2 or pioglitazone reduced basal and TNF--stimulated MCP-1 expression at mRNA and protein levels at 24 h under normoxia. MCP-1 reduction rates at basal mRNA and protein levels were slightly but significantly lower during hypoxia than normoxia (9 vs 69% and 36 vs 42%, respectively, for 15d-PGJ2, and 0 vs 34% and 12 vs 21%, respectively, for pioglitazone). Finally, a specific inhibitor for PPAR-, GW9662, weakened the MCP-1-decreasing effect of 15d-PGJ2 by about 30%, under basal conditions, while it abolished the effect of pioglitazone almost completely.
Conclusions. Hypoxia-induced loss of function of PPAR- reduces anti-inflammatory effects of PPAR- activation, possibly modulating inflammatory responses in the diseased kidney.
Keywords: HIF-1; human proximal tubular cells; hypoxia, MCP-1; PPAR; TNF-
Received for publication: 6. 5.06
Accepted in revised form: 23.11.06
CiteULike 
Connotea 
Del.icio.us What's this?
Related articles in NDT:
- In this issue ...
NDT 2007 22: i.[Extract] [FREE Full Text]
This article has been cited by other articles:
|
|
 |
|
  C. Guignabert, C. M. Alvira, T.-P. Alastalo, H. Sawada, G. Hansmann, M. Zhao, L. Wang, N. El-Bizri, and M. Rabinovitch Tie2-mediated loss of peroxisome proliferator-activated receptor-{gamma} in mice causes PDGF receptor-{beta}-dependent pulmonary arterial muscularization Am J Physiol Lung Cell Mol Physiol, December 1, 2009; 297(6): L1082 - L1090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kroening, E. Neubauer, J. Wessel, M. Wiesener, and M. Goppelt-Struebe Hypoxia interferes with connective tissue growth factor (CTGF) gene expression in human proximal tubular cell lines Nephrol. Dial. Transplant., November 1, 2009; 24(11): 3319 - 3325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kimura, X. Li, K. Torii, T. Okada, N. Takahashi, H. Fujii, S. Ishihara, and H. Yoshida A natural PPAR-{gamma} agonist, 15-deoxy-delta 12,14-prostaglandin J2, may act as an enhancer of PAI-1 in human proximal renal tubular cells under hypoxic and inflammatory conditions Nephrol. Dial. Transplant., August 1, 2008; 23(8): 2496 - 2503. [Abstract] [Full Text] [PDF]
|
|