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Coordinate regulation between the nuclear receptor peroxisome proliferator-activated receptor-γ and cyclooxygenase-2 in renal epithelial cells.

Abstract：

:The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors involved in lipid metabolism and glucose utilization, in cell growth, differentiation and apoptosis, and in the regulation of pro-inflammatory genes expression such as cyclooxygenase-2 (COX-2). PPARγ is the main isoform in the renal inner medulla where it is believed to possess nephroprotective actions. In this kidney zone, COX-2 acts as an osmoprotective gene and its expression is modulated by changes in interstitial osmolarity. In the present work we evaluated whether hyperosmolar-induced COX-2 expression is modulated by PPARγ in renal epithelial cells MDCK subjected to high NaCl medium. The results presented herein show that ligand-activated PPARγ repressed COX-2 expression. But more important, the present findings show that hyperosmolar medium decreased PPARγ protein and increases the PPARγ phosphorylated form, which is inactive. ERK1/2 and p38 activation precedes PPARγ disappearance and induced-COX-2 expression. Therefore, the decrease in PPARγ expression is required for hyperosmotic induction of COX-2. We also found that PGE2, the main product of COX-2 in MDCK cells, induced these changes in PPARγ protein. Our results may alert on the long term use of thiazolidinediones (TZD) since they could affect renal medullary function that depends on COX-2 for cellular protection against osmotic stress.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Casali CI,Weber K,Faggionato D,Gómez EM,Tome MC

doi

10.1016/j.bcp.2014.06.002

subject

Has Abstract

pub_date

2014-08-15 00:00:00

pages

432-9

issue

4

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(14)00332-3

journal_volume

90

pub_type

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