mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis.
mPGES-1 null mice are resistant to bleomycin-induced skin fibrosis.
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DOI：
10.1186/ar3226
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发表时间：
2011
影响因子：
4.9
通讯作者：
Kapoor M
中科院分区：
文献类型：
--
作者：
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
微粒体前列腺素E2合成酶-1(mPGES-1)是一种诱导性酶，作用于环氧合酶(COX)下游，特异性催化前列腺素(PG)H2转化为PGE2。MPGES-1在炎症、疼痛和关节炎中起关键作用；然而，mPGES-1在纤维化形成中的作用很大程度上是未知的。在这里，我们使用mPGES-1缺陷小鼠来研究mPGES-1在皮肤硬皮病小鼠模型中的作用。将野生型(WT)和mPGES-1基因缺失的小鼠复制成博莱霉素皮肤硬皮病模型。用免疫印迹法检测mPGES-1在硬皮病成纤维细胞和博莱霉素暴露小鼠成纤维细胞中的表达。组织学检测纤维化程度、真皮厚度、炎症反应、胶原含量及α-平滑肌肌动蛋白(α-SMA)阳性细胞数。同时测定胶原特异性氨基酸羟脯氨酸的含量。与正常皮肤成纤维细胞相比，系统性硬化症(SSC)成纤维细胞和博莱霉素暴露小鼠的mPGES-1蛋白表达增加。与WT小鼠相比，mPGES-1基因缺失的小鼠对博莱霉素诱导的炎症、皮肤增厚、胶原生成和肌成纤维细胞形成具有抵抗力。博莱霉素诱导的皮肤纤维化需要mPGES-1的表达。抑制mPGES-1可能是减缓皮肤硬化发展的一种可行的方法，也是控制纤维化发生的潜在治疗靶点。
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.
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影响因子：
4.9
作者：
Kojima F;Naraba H;Miyamoto S;Beppu M;Aoki H;Kawai S
通讯作者：
Kawai S
影响因子：
4.8
作者：
Abraham, DJ;Xu, SW;Leask, A
通讯作者：
Leask, A
影响因子：
4.4
作者：
Claveau, D;Sirinyan, M;Mancini, JA
通讯作者：
Mancini, JA
DOI：
10.1073/pnas.96.13.7220
发表时间：
1999-06-22
影响因子：
11.1
作者：
Jakobsson, PJ;Thorén, S;Samuelsson, B
通讯作者：
Samuelsson, B
影响因子：
6
作者：
Liu, JY;Brass, DM;Brody, AR
通讯作者：
Brody, AR