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https://hdl.handle.net/2440/43813
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Type: | Journal article |
Title: | Chronic colitis due to an epithelial barrier defect: the role of kindlin-1 isoforms |
Author: | Kern, J. Herz, C. Haan, E. Moore, D. Nottelmann, S. von Lilien, T. Greiner, P. Schmitt-Graeff, A. Opitz, O. Bruckner-Tuderman, L. Has, C. |
Citation: | Journal of Pathology, 2007; 213(4):462-470 |
Publisher: | John Wiley & Sons Ltd |
Issue Date: | 2007 |
ISSN: | 0022-3417 1096-9896 |
Statement of Responsibility: | JS Kern, C Herz, E Haan, D Moore, S Nottelmann, T von Lilien, P Greiner, A Schmitt-Graeff, OG Opitz, L Bruckner-Tuderman and C Has |
Abstract: | Kindlin-1 is an epithelium-specific phosphoprotein and focal adhesion adaptor component. Mutations in the corresponding gene (KIND1) cause Kindler syndrome (KS), which is manifested by skin blistering, poikiloderma, photosensitivity and carcinogenesis. Some patients also exhibit gastrointestinal symptoms, but it has remained unclear whether these represent a feature of Kindler syndrome or a coincidence. We examined kindlin-1 in human gastrointestinal epithelia and showed that it is involved in the aetiopathology of Kindler syndrome-associated colitis. Kindlin-1 expression was assessed by indirect immunofluorescence, western blot and RT-PCR. Kindlin-1 is expressed in oral mucosa, colon and rectum. Both the full-length 74 kDa kindlin-1 protein and a 43 kDa isoform were detected in CaCo2 cells, the latter resulting from alternative splicing. In the first months of life, patients (homozygous for null mutations) had severe intestinal involvement with haemorrhagic diarrhoea and showed morphological features of severe ulcerative colitis. Later in childhood, histopathology demonstrated focal detachment of the epithelium in all segments of the colon, chronic inflammation and mucosal atrophy. These findings define an intestinal phenotype for Kindler syndrome as a consequence of a primary epithelial barrier defect. The different clinical intestinal manifestations in Kindler syndrome patients may be explained by partial functional compensation of kindlin-1 deficiency by the intestinal isoform or by the presence of truncated mutant kindlin-1. |
Keywords: | Intestinal Mucosa Humans Colitis, Ulcerative Skin Diseases, Genetic Blister Syndrome Chronic Disease Membrane Proteins Neoplasm Proteins Protein Isoforms Fluorescent Antibody Technique, Indirect Reverse Transcriptase Polymerase Chain Reaction Mutation Child Infant, Newborn Female Male Rothmund-Thomson Syndrome |
Description: | Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
DOI: | 10.1002/path.2253 |
Published version: | http://dx.doi.org/10.1002/path.2253 |
Appears in Collections: | Aurora harvest Medicine publications |
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