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The amount of keratins matters for stress protection of the colonic epithelium

Asghar, M. Nadeem; Silvander, Jonas S. G.; Helenius, Terhi O.; L�hdeniemi, Iris A. K.; Alam, Catharina; Fortelius, Lina E.; Holmsten, Rickard O.; Toivola, Diana M.

Authors

M. Nadeem Asghar

Jonas S. G. Silvander

Terhi O. Helenius

Iris A. K. L�hdeniemi

Lina E. Fortelius

Rickard O. Holmsten

Diana M. Toivola



Abstract

Keratins (K) are important for epithelial stress protection as evidenced by keratin mutations predisposing to human liver diseases and possibly inflammatory bowel diseases. A role for K8 in the colon is supported by the ulcerative colitis-phenotype with epithelial hyperproliferation and abnormal ion transport in K8-knockout (K8-/-) mice. The heterozygote knockout (K8+/-) colon appears normal but displays a partial ion transport-defect. Characterizing the colonic phenotype we show that K8+/- colon expresses ~50% less keratins compared to K8 wild type (K8+/+) but de novo K7 expression is observed in the top-most cells of the K8+/- and K8-/- crypts. The K8+/- colonic crypts are significantly longer due to increased epithelial hyperproliferation, but display no defects in apoptosis or inflammation in contrast to K8-/-. When exposed to colitis using the dextran sulphate sodium-model, K8+/- mice showed higher disease sensitivity and delayed recovery compared to K8+/+ littermates. Therefore, the K8+/- mild colonic phenotype correlates with decreased keratin levels and increased sensitivity to experimental colitis, suggesting that a sufficient amount of keratin is needed for efficient stress protection in the colonic epithelia.

Journal Article Type Article
Acceptance Date Apr 15, 2015
Online Publication Date May 22, 2015
Publication Date 2015
Deposit Date May 26, 2022
Publicly Available Date Jun 28, 2023
Journal PLOS ONE
Print ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 10
Issue 5
Article Number e0127436
DOI https://doi.org/10.1371/journal.pone.0127436
Public URL http://researchrepository.napier.ac.uk/Output/2869938
Related Public URLs https://europepmc.org/articles/PMC4441500

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