(21) Colonic keratins are upregulated in severe lesions of IBD and downregulated in microscopic colitis
Författare/Medförfattare
Victor Nielsen [1,2, 3], Lauri Polari [1,2], Santeri Anttila [4], Markku Kallajoki [4,5], Markku Voutilainen [4,5], Diana M. Toivola [1,2]
Affiliates
Cell Biology, Biosciences [1] and InFLAMES Research Flagship Center [2], Åbo Akademi University, Turku, Finland, Department of Pathology, Wellbeing services county of Satakunta, Pori, Finland [3], University of Turku [4], Turku University Hospital, Turku, Finland [5].
Abstract
Background
Keratins (K) are a major group of cytoskeletal proteins in epithelial cells where they support cellular and tissue integrity. Aberrant keratin expression is found in inflammatory disorders, especially in the skin. Recently, we found K7 to be upregulated in IBD. In this study, we focus on the expression changes of main colon keratins, which are K8, K18, K19 and K20.
Methods
Formalin fixated paraffin embedded (FFPE) samples collected from patients with UC (N=15), CD (N=11), microscopic colitis (MC) (N=18), and normal colon tissue (N=12) were obtained from Auria Biobank (Turku, Finland). Regions of interests (ROIs) were scored for their histopathological characteristics. Immunohistochemical (IHC) staining for K8, K18, K19 and K20 was performed using standardized hospital equipment and reagents. Scanned slides were analysed for cellular keratin expression using Qupath digital image analysis software. Diagnosis, histopathological characteristics and clinical parameters were correlated with keratin expression.
Results
The IHC stainings demonstrated a significant upregulation of K8, K18, K19 and K20 in UC and K18 in CD. The increase was higher in general in UC when comparing the two subtypes of IBD. On the other hand, colonic keratins expression was decreased in MC. High expression of colonic keratins correlated with severe IBD-associated histopathological features like epithelial deformity, atrophy and inflammation activity. The colonic keratin expression was also significantly higher in patients with poorer responsiveness to IBD drug treatment.
Conclusion
Our study further highlights the importance that sustained keratin levels have for tissue integrity. The biological role of K upregulation in IBD require further research, since keratin concentration changes and de novo expression have recently been reported in other diseases as well. Furthermore, low cellular keratin levels could be associated with impaired intestinal barrier and increased epithelial permeability present in MC.