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

Tracy Coelho,Anthony P Williams,Annie Griffin,James J Ashton,Bhumita Vadgama,Akshay Batra,Alisher Khojanazarov,Eva Sonnenberg-Riethmacher,К С Адрисова ,R Mark Beattie ,Michael Stanton ,Imogen S Stafford ,Nadeem Afzal ,Sarah Ennis,Rachel Haggarty,Aiymkul Ashimkhanova,Enrico Mossotto,Anton Borissenko,Yifang Gao,Saida Mukanova,Dieter Riethmacher

doi:10.1038/s41598-021-85096-7

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.

Highlights

The precise role of periostin, an extra-cellular matrix protein, in inflammatory bowel disease (IBD) is unclear
Recent studies have implicated its role in inflammatory bowel disease (IBD)[7,8], the precise mechanisms through which it influences the immune signalling pathways in IBD remains unclear, with varying results observed in patients and animal m odels[7,8,9]
Our study explores the feasibility of using periostin to assess disease activity in paediatric inflammatory bowel disease, and its role in inflammation and repair.The study assesses plasma periostin levels in pIBD, investigating its relationship with disease activity, surgical outcomes and genomic variation

Summary

Introduction

The precise role of periostin, an extra-cellular matrix protein, in inflammatory bowel disease (IBD) is unclear. We investigated periostin in paediatric IBD including its relationship with disease activity, clinical outcomes, genomic variation and expression in the colonic tissue. 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. Recent studies have implicated its role in inflammatory bowel disease (IBD)[7,8], the precise mechanisms through which it influences the immune signalling pathways in IBD remains unclear, with varying results observed in patients and animal m odels[7,8,9]. Aberrant function of the NF-κB pathway, a pivotal mediator of inflammatory immune responses, has long been considered to be a key factor in the development of IBD10. As periostin is functionally connected to the NF-κB pathway, in inflammatory states, investigating the functionality of this rather obscure protein will be an important step forward for a better understanding of IBD7,13,14

Methods

Results

Conclusion