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Plectin ensures intestinal epithelial integrity and protects colon against colitis
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SYSNO ASEP 0542952 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Plectin ensures intestinal epithelial integrity and protects colon against colitis Author(s) Krausová, Alžběta (UMG-J)
Burešová, Petra (UMG-J)
Sarnová, Lenka (UMG-J)
Oyman-Eyrilmez, Gizem (UMG-J)
Škarda, J. (CZ)
Wohl, P. (CZ)
Bajer, L. (CZ)
Sticová, E. (CZ)
Bartoňová, L. (CZ)
Pácha, Jiří (FGU-C) RID, ORCID
Koubková, Gizela (UMG-J)
Procházka, Jan (UMG-J) ORCID
Sporrer, M. (DE)
Durrbeck, C. (DE)
Stehlíková, Zuzana (MBU-M)
Vít, M. (CZ)
Ziolkowska, N. (CZ)
Sedláček, Radislav (UMG-J) RID
Jirák, D. (CZ)
Kverka, Miloslav (MBU-M) RID, ORCID
Wiche, G. (AT)
Fabry, B. (DE)
Kořínek, Vladimír (UMG-J) RID
Gregor, Martin (UMG-J) RID, ORCIDNumber of authors 24 Source Title Mucosal Immunology. - : Springer - ISSN 1933-0219
Roč. 14, č. 3 (2021), s. 691-702Number of pages 12 s. Publication form Online - E Language eng - English Country US - United States Keywords colitis ; plectin ; intestinal mucosa Subject RIV EB - Genetics ; Molecular Biology OECD category Immunology Subject RIV - cooperation Institute of Microbiology - Microbiology, Virology R&D Projects NV17-31538A GA MZd - Ministry of Health (MZ) GA17-09869S GA ČR - Czech Science Foundation (CSF) GJ20-16520Y GA ČR - Czech Science Foundation (CSF) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LTC17063 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LO1419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001775 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 ; FGU-C - RVO:67985823 ; MBU-M - RVO:61388971 UT WOS 000625614200003 EID SCOPUS 85102021983 DOI https://doi.org/10.1038/s41385-021-00380-z Annotation Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC, Ple(Delta IEC)) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal alpha 6 beta 4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the Ple(Delta IEC) colon. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2022 Electronic address https://www.nature.com/articles/s41385-021-00380-z
Number of the records: 1