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

作者：McCann Matthew R; Monemdjou Roxana; Ghassemi Kakroodi Parisa; Fahmi Hassan; Perez Gemma; Liu Shangxi; Xu Shi wen; Parapuram Sunil K; Kojima Fumiaki; Denton Christopher P; Abraham David J; Martel Pelletier Johanne; Crofford Leslie J; Leask Andrew; Kapoor Mohit^*

来源：Arthritis Research and Therapy, 2011, 13(1): R6.

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) 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.

• 出版日期2011