title: Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers.
abstract: 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-β, 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.
authors.affiliation: Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ae
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohno
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Hattori
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kanako
authors.initials: K
authors.lastname: Hosono
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Minamino
authors.forename: Takehito
authors.initials: T
authors.lastname: Sato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
authors.forename: Masataka
authors.initials: M
authors.lastname: Majima
mesh_terms: D019342:Acetic Acid; D000704:Analysis of Variance; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D000071876:Prostaglandin-E Synthases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000503:physiopathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D019342:Acetic Acid