title: The amount of keratins matters for stress protection of the colonic epithelium.
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.
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, and Turku Center for Disease Modeling, Turku, Finland.
authors.forename: M Nadeem
authors.initials: MN
authors.lastname: Asghar
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, and Turku Center for Disease Modeling, Turku, Finland.
authors.forename: Jonas S G
authors.initials: JS
authors.lastname: Silvander
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, and Turku Center for Disease Modeling, Turku, Finland.
authors.forename: Terhi O
authors.initials: TO
authors.lastname: Helenius
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, and Turku Center for Disease Modeling, Turku, Finland.
authors.forename: Iris A K
authors.initials: IA
authors.lastname: Lähdeniemi
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, and Turku Center for Disease Modeling, Turku, Finland.
authors.forename: Catharina
authors.initials: C
authors.lastname: Alam
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, and Turku Center for Disease Modeling, Turku, Finland.
authors.forename: Lina E
authors.initials: LE
authors.lastname: Fortelius
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, and Turku Center for Disease Modeling, Turku, Finland.
authors.forename: Rickard O
authors.initials: RO
authors.lastname: Holmsten
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University, and Turku Center for Disease Modeling, Turku, Finland.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Toivola
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D016264:Dextran Sulfate; D007249:Inflammation / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport / Q000235:genetics; D053552:Keratin-7 / Q000235:genetics / Q000378:metabolism*; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D053552:Keratin-7; D053533:Keratin-8; D017382:Reactive Oxygen Species; D016264:Dextran Sulfate