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
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
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.
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