Journal
ARTHRITIS RESEARCH & THERAPY
Volume 13, Issue 1, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/ar3226
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Funding
- CIHR
- Canadian Institutes of Health Research
- Canadian Foundation for Innovation
- Fonds de la Recherche en Sante du Quebec
- University of Montreal Hospital Research Centre (CR-CHUM)
- National Institutes of Health
- Ontario Thoracic Society
- Arthritis Research Campaign
- Reynaud's and Scleroderma Association
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR049010] Funding Source: NIH RePORTER
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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) H-2 to PGE(2). 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 alpha-smooth muscle actin (alpha-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.
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