Matricellular Protein Periostin Mediates Intestinal Inflammation through the Activation of Nuclear Factor κB Signaling

• Published in: PloS one 2016-02, Vol.11 (2), p.e0149652-e0149652
• Main Authors: Koh, Seong-Joon, Choi, Younjeong, Kim, Byeong Gwan, Lee, Kook Lae, Kim, Dae Woo, Kim, Jung Ho, Kim, Ji Won, Kim, Joo Sung
• Format: Article
• Language: English
• Subjects: Activation; Acute Disease; Animals; Antibodies, Neutralizing - pharmacology; Biology and Life Sciences; Cell Adhesion Molecules - metabolism; Cell Line; Cell surface; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Colon; Colon - metabolism; Colon - pathology; Cytokines - biosynthesis; Deoxyribonucleic acid; Dextran; Dextran sulfate; Disease Models, Animal; DNA; Enterocytes - drug effects; Enterocytes - metabolism; Enterocytes - pathology; Epithelial cells; Gastroenterology; Gene expression; Gene Silencing - drug effects; Homeostasis; Hospitals; Humans; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammatory bowel disease; Inflammatory bowel diseases; Integrin alphaV - metabolism; Interleukin 8; Interleukin-8 - metabolism; Internal medicine; Intestine; Intestines - pathology; Male; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mucosa; NF-kappa B - metabolism; NF-κB protein; Oral administration; Otolaryngology; Patients; Protein Binding - drug effects; Proteins; Recombinant Proteins - administration & dosage; Rectum; Research and Analysis Methods; Rodents; Signal transduction; Signal Transduction - drug effects; Sodium; Sulfate; Sulfonic acid; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ulcerative colitis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0149652

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.