mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis
- Equal contributors
1 The Canadian Institute of Health Research Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building, London, Ontario, N6A 5C1, Canada
2 Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CR-CHUM) and Department of Medicine, University of Montreal, 1560 Rue Sherbrooke Est, Montréal, Québec, H2L 4M1, Canada
3 Centre for Rheumatology, Department of Medicine, University College London (Royal Free Campus), Rowland Hill Street, London, NW3 2PF, UK
4 Division of Rheumatology, Department of Internal Medicine, University of Kentucky, 740 S. Limestone Street, J-509 Kentucky Clinic, Lexington, KY 40536, USA
Arthritis Research & Therapy 2011, 13:R6 doi:10.1186/ar3226Published: 25 January 2011
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.
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.
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.
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.