mPGES-1 Null Mice Are Resistant to Bleomycin-induced Skin Fibrosis

Authors

Matthew R. McCann, The University of Western Ontario
Roxana Monemdjou, University of Montreal
Parisa Ghassemi-Kakroodi, The University of Western Ontario
Hassan Fahmi, The University of Western Ontario
Gemma Perez, University of Montreal
Shangxi Liu, The University of Western Ontario
Xu Shi-Wen, University College London
Sunil K Parapuram, The University of Western Ontario
Fumiaki Kojima, University of Kentucky
Christopher P Denton, University College London
David J Abraham, University College London
Johanne Martel-Pelletier, University of Montreal
Leslie J Crofford, University of Kentucky
Andrew Leask, The University of Western Ontario
Mohit Kapoor, University of Montreal

Document Type

Article

Publication Date

1-25-2011

Journal

Arthritis Research & Therapy

Volume

13

Issue

6

URL with Digital Object Identifier

http://dx.doi.org/10.1186/ar3226

Abstract

INTRODUCTION: Microsomal prostaglandin E2 synthase-1 (mPGES-1) is an inducible enzyme that acts downstream of cyclooxygenase (COX) to specifically catalyze the conversion of prostaglandin (PG) H2 to PGE2. mPGES-1 plays a key role in inflammation, pain and arthritis; however, the role of mPGES-1 in fibrogenesis is largely unknown. Herein, we examine the role of mPGES-1 in a mouse model of skin scleroderma using mice deficient in mPGES-1.

METHODS: Wild type (WT) and mPGES-1 null mice were subjected to the bleomycin model of cutaneous skin scleroderma. mPGES-1 expressions in scleroderma fibroblasts and in fibroblasts derived from bleomycin-exposed mice were assessed by Western blot analysis. Degree of fibrosis, dermal thickness, inflammation, collagen content and the number of α-smooth muscle actin (α-SMA)-positive cells were determined by histological analyses. The quantity of the collagen-specific amino acid hydroxyproline was also measured.

RESULTS: Compared to normal skin fibroblasts, mPGES-1 protein expression was elevated in systemic sclerosis (SSc) fibroblasts and in bleomycin-exposed mice. Compared to WT mice, mPGES-1-null mice were resistant to bleomycin-induced inflammation, cutaneous thickening, collagen production and myofibroblast formation.

CONCLUSIONS: mPGES-1 expression is required for bleomycin-induced skin fibrogenesis. Inhibition of mPGES-1 may be a viable method to alleviate the development of cutaneous sclerosis and is a potential therapeutic target to control the onset of fibrogenesis.

Notes

Correction to this article is available at: http://dx.doi.org/10.1186/ar3285