mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis

Authors

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

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.

Document Type

Article

Publication Date

1-25-2011

Notes/Citation Information

Published in Arthritis Research & Therapy, v. 13, R6.

© 2011 McCann et al.; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A correction for this article is available as an additional file listed below.

Digital Object Identifier (DOI)

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

Repository Citation

McCann, Matthew R.; Monemdjou, Roxana; Ghassemi-Kakroodi, Parisa; Fahmi, Hassan; Perez, Gemma; Liu, Shangxi; Shi-Wen, Xu; Parapuram, Sunil K.; Kojima, Fumiaki; Denton, Christopher P.; Abraham, David J.; Martel-Pelletier, Johanne; Crofford, Leslie J.; Leask, Andrew; and Kapoor, Mohit, "mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis" (2011). Internal Medicine Faculty Publications. 16.
https://uknowledge.uky.edu/internalmedicine_facpub/16