Expression of Cytokine-Coding Genes BMP8B, LEFTY1 and INSL5 Could Distinguish between Ulcerative Colitis and Crohn's Disease.

Daša Jevšinek Skok,Miha Jerala,Nina Hauptman,Nina Zidar

doi:10.3390/genes12101477

Daša Jevšinek Skok, Miha Jerala + Show 2 more

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https://doi.org/10.3390/genes12101477

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Abstract

Ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by an imbalance between pro-inflammatory and anti-inflammatory cytokines, interfering with the resolution of inflammation. Due to the crucial role of cytokines, new insights into their profiles in UC and CD would help to improve our understanding of pathogenesis and enable the development of new treatment modalities. We provide an expression profile of cytokines in UC and CD, using bioinformatics approach, and experimental validation of expression of the selected genes. We retrieved data and analyzed the cytokine gene expression profiles of UC and CD. From ten genes with inverse expression, common to CD and UC, BMP8B, LEFTY1 and INSL5 were selected for gene expression experimental validation. Experimentally, BMP8B and INSL5 were down-regulated in both CD and UC but followed the bioinformatics trend. The expression of genes LEFTY1 and BMP8B was statistically significant when comparing UC and CD in colon and the expression of gene LEFTY1 showed statistical significance when CD in ileum and colon were compared. Using the bioinformatics approach and experimental validation, we found differences in expression profiles between UC and CD for INSL5, LEFTY1 and BMP8B. These three promising candidate genes need to be further explored at different levels, such as DNA methylation and protein expression, to provide more evidence on their potential diagnostic role in CD and UC.

Highlights

Despite significant progress in our understanding of both major forms of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), many questions remain unresolved, such as the exact pathogenesis and the reason for different macroscopic, microscopic, and clinical features of UC and CD [1,2]
We selected INSL5, which had the largest difference in logFC among UC and CD (∆logFC = 4.49), BMP8B with the smallest difference in logFC among CD and UC (∆logFC = 1.37), and LEFTY1, where the difference between UC and CD was somewhere in the middle (∆logFC = 2.30) (Table 1)
Our experimental results show that BMP8B and INSL5 are both down-regulated in both CD compared to normal (BMP8B logFC = −1.21, p < 0.001; INSL5 logFC = −2.26, p = 0.048), and UC compared to normal

Summary

Introduction

Despite significant progress in our understanding of both major forms of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), many questions remain unresolved, such as the exact pathogenesis and the reason for different macroscopic, microscopic, and clinical features of UC and CD [1,2]. Both UC and CD develop as a result of an interaction between genetic and environmental factors, which promotes an excessive response of gut-associated immune system against the gut microbiota. The aim of the present study is to provide an expression profile of cytokines in UC and CD, using bioinformatics approach, and experimental validation of the selected cytokine coding genes

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