title: Protective effect of endogenous PPARgamma against acute gastric mucosal lesions associated with ischemia-reperfusion.
abstract: Acute gastric mucosal lesions (AGMLs) are an important cause of gastrointestinal bleeding. Herein, we demonstrate that peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of a nuclear receptor family, functions as an endogenous anti-inflammatory pathway in a murine model of AGML induced by ischemia-reperfusion (I/R). Treatment with specific PPARgamma ligands such as BRL-49653, pioglitazone, or troglitazone was examined in a model of AGML induced by I/R. PPARgamma-deficient and wild-type mice were also examined for their response to I/R in stomach. Specific PPARgamma ligands exhibited dramatic and rapid protection against AGML formation associated with I/R in mice in a dose-dependent manner. In contrast, the AGML induced by I/R in PPARgamma-deficient mice was more severe than that observed in wild-type mice. Administration of the PPARgamma ligand significantly inhibited the upregulation of TNF-alpha, ICAM-1, inducible nitric oxide synthase, apoptosis, and nitrotyrosine formation induced by I/R in the stomach. These data indicate that an endogenous pathway associated with PPARgamma plays an important role in the pathogenesis of I/R-associated injury in the stomach.
authors.affiliation: Gastroenterology Division, Thorn 1419, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Wada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujisawa
authors.forename: Emi
authors.initials: E
authors.lastname: Ohsawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matsuhashi
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Saubermann
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakajima
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D013270:Stomach / Q000098:blood supply*; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
chemical_list: D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse