Expression profile of the matricellular protein periostin in paediatric inflammatory bowel disease

Abstract

The precise role of periostin, an extra-cellular matrix protein, in inflammatory bowel disease (IBD) is unclear. Here, we investigated periostin in paediatric IBD including its relationship with disease activity, clinical outcomes, genomic variation and expression in the colonic tissue. Plasma periostin was analysed using ELISA in 144 paediatric patients and 38 controls. Plasma levels were assessed against validated disease activity indices in IBD and clinical outcomes. An immuno-fluorescence for periostin and detailed isoform-expression analysis in the colonic tissue was performed in 23 individuals. We integrated a whole-gene based burden metric ‘GenePy’ to assess the impact of variation in POSTN and 23 other genes functionally connected to periostin. We found that plasma periostin levels were significantly increased during remission compared to active Crohn’s disease. The immuno-fluorescence analysis demonstrated enhanced peri-cryptal ring patterns in patients compared to controls, present throughout inflamed, as well as macroscopically non-inflamed colonic tissue. Interestingly, the pattern of isoforms remained unchanged during bowel inflammation compared to healthy controls. In addition to its role during the inflammatory processes in IBD, periostin may have an additional prominent role in mucosal repair. Additional studies will be necessary to understand its role in the pathogenesis, repair and fibrosis in IBD.

Periostin in Allergy and Inflammation

“…Periostin has been shown to be upregulated in the subepithelial region in asthma (10), AD (37,49), allergic conjunctivitis (AC) (52), eosinophilic esophagitis (EoE) (31) and familial idiopathic pulmonary fibrosis (IPF) (47,48). Periostin is also upregulated in chronic inflammations such as IBD and rheumatoid arthritis (RA) (16,28,29). Interestingly, IL-24 and STAT-3 as downstream effectors of periostin are enhancing the epithelial-barrier dysfunction thereby further fuelling the inflammatory process (92).…”

“…In a recent study, all expressed periostin isoforms in the small intestine were described. Interestingly, periostin variants 1, 5, 6 and 7 were detected but not the full length (see details in Figure 3) (28). Periostin has also been linked to the increased risk of colitis-associated colorectal cancer in a mouse model and its expression is also elevated in IBD patients (30).…”

“…Epidemiologic studies highlight the increased risk of colorectal cancer (CRC) in IBD and generally link this risk to the pro-neoplastic effects of chronic intestinal inflammation (118). Given the altered expression of periostin in acute IBD and during remission in human patients (28), and the link to cancer progression in general as well as in CRC in mouse models, it is tempting to speculate that periostin may likely play a similar role in CRC in human patients (68,74,81).…”

“…In a recent study, an inverse association between circulating periostin and disease activity index in pediatric Crohn's disease has been found, suggesting a more prominent role in repair rather than fuelling inflammatory cascades in this disease. The precise mechanism behind the significantly increased plasma levels of the protein during remission compared to active disease remains unclear (28). Periostin levels have been shown to be elevated in serum of asthmatic patients.…”

Role of periostin in inflammatory bowel disease development and synergistic effects mediated by the CCL5–CCR5 axis

“…Periostin contains an N-terminal secretory signal peptide, followed by a cysteine-rich domain (EMI domain), four FAS1 domains, and a hydrophilic carboxy-terminal domain (CTD) that shows a remarkable amount of alternative splicing ( 12 , 14 ). Recent studies have demonstrated that periostin plays a role in IBD; however, the precise mechanisms through which it influences the immune signaling pathways in IBD in patients and animal models are still not fully understood ( 15 – 18 ).…”