title: Matricellular Protein Periostin Mediates Intestinal Inflammation through the Activation of Nuclear Factor κB Signaling.
abstract: Periostin is a matricellular protein that interacts with various integrin molecules on the cell surface. Although periostin is expressed in inflamed colonic mucosa, its role in the regulation of intestinal inflammation remains unclear. We investigated the role of periostin in intestinal inflammation using Postn-deficient (Postn-/-) mice. Intestinal epithelial cells (IECs) were transfected by Postn small interfering RNAs. Periostin expression was determined in colon tissue samples from ulcerative colitis (UC) patients. Oral administration of dextran sulfate sodium (DSS) or rectal administration of trinitrobenzene sulfonic acid, induced severe colitis in wild-type mice, but not in Postn-/- mice. Administration of recombinant periostin induced colitis in Postn-/- mice. The periostin neutralizing-antibody ameliorated the severity of colitis in DSS-treated wild-type mice. Silencing of Postn inhibited inteleukin (IL)-8 mRNA expression and NF-κB DNA-binding activity in IECs. Tumor necrosis factor (TNF)-α upregulated mRNA expression of Postn in IECs, and recombinant periostin strongly enhanced IL-8 expression in combination with TNF-α, which was suppressed by an antibody against integrin αv (CD51). Periostin and CD51 were expressed at significantly higher levels in UC patients than in controls. Periostin mediates intestinal inflammation through the activation of NF-κB signaling, which suggests that periostin is a potential therapeutic target for inflammatory bowel disease.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seong-Joon
authors.initials: SJ
authors.lastname: Koh
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Younjeong
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Byeong Gwan
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kook Lae
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Dae Woo
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Joo Sung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D039564:Integrin alphaV / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D015815:Cell Adhesion Molecules; D016207:Cytokines; D039564:Integrin alphaV; D016209:Interleukin-8; D016328:NF-kappa B; C512835:POSTN protein, human; C082838:Postn protein, mouse; D011994:Recombinant Proteins