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

McCann MR, Monemdjou R, Ghassemi-Kakroodi P, Fahmi H, Perez G, Liu S, Shi-Wen X, Parapuram SK, Kojima F, Denton CP, Abraham DJ, Martel-Pelletier J, Crofford LJ, Leask A, Kapoor M
Arthritis Res Ther. 2011 13 (1): R6

PMID: 21266028 · PMCID: PMC3546456 · DOI:10.1186/ar3226

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.

MeSH Terms (16)

Animals Antibiotics, Antineoplastic Bleomycin Blotting, Western Disease Models, Animal Female Fibroblasts Fibrosis Fluorescent Antibody Technique Immunohistochemistry Intramolecular Oxidoreductases Male Mice Mice, Knockout Prostaglandin-E Synthases Scleroderma, Systemic

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