Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers
Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers
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DOI：
10.1152/ajpgi.00013.2010
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发表时间：
2010-11-01
影响因子：
4.5
通讯作者：
Majima, Masataka
中科院分区：
文献类型：
--
作者：
Ae, Takako;Ohno, Takashi;Majima, Masataka
Ae T，Ohno T，Hattori Y，Suzuki T，Hosono K，Minamino T，Sato T，Uematsu S，Akira S，Koizumi W，Majima M.微粒体前列腺素E合酶-1在促进血管生成和胃溃疡愈合中的作用。美国生理学杂志胃肠和肝脏生理学299：G1139-G1146，2010年。首次发表于2010年9月2日; doi：10.1152/ajpgi.00013.2010.-前列腺素E-2在各种病理生理事件中的重要性强调了了解PGE酶（PGES）在体内作用的必要性。然而，还没有关于微粒体PGES-1（mPGES-1）的功能相关性的胃溃疡的生理愈合过程，或血管生成，这是必不可少的愈合过程。在这份报告中，我们使用mPGES-1敲除小鼠（mPGES-1 KO小鼠）及其野生型（WT）小鼠测试了mPGES-1是否在胃溃疡愈合和血管生成增强中发挥作用。胃溃疡是通过100%乙酸的血清学应用诱导的，并且此后测量溃疡的面积。与正常胃组织相比，肉芽组织中mPGES-1和环氧合酶-2被诱导。与WT相比，mPGES-1 KO小鼠中乙酸诱导的溃疡愈合显著延迟。这是伴随着减少溃疡肉芽组织中的血管生成，如通过实时PCR和肉芽组织中的微血管密度确定的CD 31 mRNA水平所估计的。与WT相比，mPGES-1 KO小鼠中测定的溃疡肉芽组织中促血管生成生长因子（如转化生长因子-β、碱性成纤维细胞生长因子和结缔组织生长因子）的mRNA水平降低。目前的研究结果表明，mPGES-1增强溃疡愈合过程和血管生成必不可少的溃疡愈合，和一个选择性mPGES-1抑制剂应谨慎使用胃溃疡患者。
Ae T, Ohno T, Hattori Y, Suzuki T, Hosono K, Minamino T, Sato T, Uematsu S, Akira S, Koizumi W, Majima M. Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers. Am J Physiol Gastrointest Liver Physiol 299: G1139-G1146, 2010. First published September 2, 2010; doi: 10.1152/ajpgi.00013.2010.-The importance of prostaglandin E-2 in various pathophysiological events emphasizes the necessity of understanding the role of PGE synthases (PGESs) in vivo. However, there has been no report on the functional relevance of microsomal PGES-1 (mPGES-1) to the physiological healing processes of gastric ulcers, or to angiogenesis, which is indispensable to the healing processes. In this report, we tested whether mPGES-1 plays a role in the healing of gastric ulcers and in the enhancement of angiogenesis using mPGES-1 knockout mice (mPGES-1 KO mice) and their wild-type (WT) counterparts. Gastric ulcers were induced by the serosal application of 100% acetic acid, and the areas of the ulcers were measured thereafter. mPGES-1 together with cyclooxygenase-2 were induced in the granulation tissues compared with normal stomach tissues. The healing of acetic acid-induced ulcers was significantly delayed in mPGES-1 KO mice compared with WT. This was accompanied with reduced angiogenesis in ulcer granulation tissues, as estimated by CD31 mRNA levels determined by real-time PCR and the microvessel density in granulation tissues. The mRNA levels of proangiogenic growth factors, such as transforming growth factor-beta, basic fibroblast growth factor, and connective tissue growth factor in ulcer granulation tissues determined were reduced in mPGES-1 KO mice compared with WT. The present results suggest that mPGES-1 enhances the ulcer-healing processes and the angiogenesis indispensable to ulcer healing, and that a selective mPGES-1 inhibitor should be used with care in patients with gastric ulcers.