Effect of cyclooxygenase (COX)-2 inhibition on mouse renal interstitial fibrosis

Eur J Pharmacol. 2014 Oct 5;740:578-83. doi: 10.1016/j.ejphar.2014.06.027. Epub 2014 Jun 26.

Abstract

Unilateral ureteral obstruction (UUO) is a well-established model for the study of interstitial fibrosis in the kidney. In this study, we investigated the effects of a COX-2 inhibitor, meloxicam, on UUO-induced renal interstitial fibrosis in mice. Serum creatinine, blood urea nitrogen and urinary glucose were significantly increased by UUO. However, all of these changes were attenuated by meloxicam (1 mg/kg/day). Masson׳s trichrome staining showed that interstitial fibrosis was significantly increased by UUO, but that meloxicam also significantly diminished the area of UUO-induced fibrosis. Heat shock protein (HSP) 47 protein, a collagen-specific molecular chaperone essential for the biosynthesis of collagen molecules, and type IV collagen mRNA were increased in kidneys of UUO mice. Meloxicam reduced the expression of both HSP47 protein and type IV collagen mRNA. The phosphorylation of extracellular regulated kinase (ERK) and c-jun-N-terminal kinase (JNK) was increased by UUO, but these changes were inhibited by meloxicam. Collectively, these results suggest that COX-2 may be involved in the expression of HSP47 and type IV collagen through the phosphorylation of ERK and JNK, accelerating renal interstitial fibrosis.

Keywords: COX-2 inhibitor; Fibrosis; Heat shock protein (HSP) 47; Meloxicam (PubChem CID: 54677470); Type IV collagen; Unilateral ureteral obstruction (UUO).

MeSH terms

  • Animals
  • Collagen / genetics
  • Collagen / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Fibrosis
  • HSP47 Heat-Shock Proteins / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / drug therapy
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology*
  • Male
  • Meloxicam
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • RNA, Messenger / metabolism
  • Thiazines / pharmacology*
  • Thiazines / therapeutic use
  • Thiazoles / pharmacology*
  • Thiazoles / therapeutic use

Substances

  • Cyclooxygenase 2 Inhibitors
  • HSP47 Heat-Shock Proteins
  • RNA, Messenger
  • Serpinh1 protein, mouse
  • Thiazines
  • Thiazoles
  • Collagen
  • Mitogen-Activated Protein Kinase Kinases
  • Meloxicam