PI3K-dependent GSK3ß(Ser9)-phosphorylation is implicated in the intestinal epithelial cell wound-healing response.

URN zum Zitieren dieses Dokuments:: urn:nbn:de:bvb:355-epub-237551
DOI zum Zitieren dieses Dokuments:: 10.5283/epub.23755

Karrasch, Thomas ; Spaeth, Tanja ; Allard, Brigitte ; Jobin, Christian

Vorschau

PDF
(421kB)

Veröffentlichungsdatum dieses Volltextes: 11 Apr 2012 09:01

Alternative Links zum Volltext:Pubmed DOI

Details

Vorschau

Indiziert in

Bibliographische Daten exportieren

Zusammenfassung

Zusammenfassung

Introduction: The ability of the intestinal epithelial barrier to respond to various injurious insults is an essential component of intestinal homeostasis. However, the molecular mechanisms responsible for wound-healing and repair in the intestine are poorly understood. The glycogen synthase kinase 3 beta (GSK3 beta) has been implicated in various biological processes such as cellular motility, cell spreading and recently inflammation. Aim: To investigate the role of GSK3 beta in intestinal epithelial cell restitution. Methods: Rat intestinal epithelial IEC18 cells were serum-starved for 16 to 24h and wounded by multiple scraping. Akt(Ser473)-, GSK3 beta(Ser9)-and RelA(Ser536)-phosphorylation were determined by Western blot using specific phospho-antibodies. The inhibitors AG1478 (1 mu M) and Ly294002 (25 mM) were used to block EGF-R autophosphorylation and PI3K-activation, respectively. beta-catenin/LEF/TCF dependent transcription was determined by reporter gene assay (TOP/FOP system). C-myc gene expression was evaluated by real-time RT-PCR. GSK3 beta(-/-) mouse embryonic fibroblasts were used to characterize the role of GSK3 beta in wounding-induced cell migration. Results: Wounding induced GSK3 beta(Ser9) phosphorylation in IEC-18 cells, which led to beta-catenin accumulation as well as nuclear translocation of beta-catenin. beta-catenin stabilization/nuclear translocation led to enhanced LEF-TCF transcriptional activity and subsequent c-myc mRNA accumulation in wounded cell monolayers. Blocking PI3K/Akt signaling with Ly294002 prevented wound-induced GSK3 beta(Ser9) phosphorylation as well as beta-catenin nuclear translocation and significantly attenuated restitution. Additionally, wounding induced rapid NF-kB(Ser536) phosphorylation, which was inhibited by AG1478, but not by Ly294002. GSK3 beta(-/-) cells demonstrated significantly attenuated wound-induced restitution compared to wild-type cells. Conclusion: We conclude that PI3K-mediated GSK3 beta phosphorylation is involved in the intestinal epithelial wound-healing response. Phosphorylation of GSK3 beta may be important for intestinal restitution by promoting cell motility in response to wounding.

Nur für Besitzer und Autoren: Kontrollseite des Eintrags

Downloadstatistik

Artikel Metrik (PLOS)

Altmetric

Alternative Statistik (altmetrics)

Weitere Literatur (mittels CORE)

Details

Vorschau

Indiziert in

Bibliographische Daten exportieren

Zusammenfassung

Zusammenfassung

Downloadstatistik

Downloads

Artikel Metrik (PLOS)

Alternative Statistik (altmetrics)

Weitere Literatur (mittels CORE)

Universitätsbibliothek