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The Candidate IBD Risk Gene CCNY Is Dispensable for Intestinal Epithelial Homeostasis

The CCNY gene, which encodes cyclin Y, has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Cyclin Y promotes Wnt/β-catenin signaling and autophagy, which are critical for intestinal epithelial cell (IEC) homeostasis, and may thereby contribute to wound repair in colitis. How...

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Detalles Bibliográficos
Autores principales: Molinas, Andrea, Heil, Stéphanie, Koch, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471355/
https://www.ncbi.nlm.nih.gov/pubmed/34571979
http://dx.doi.org/10.3390/cells10092330
Descripción
Sumario:The CCNY gene, which encodes cyclin Y, has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Cyclin Y promotes Wnt/β-catenin signaling and autophagy, which are critical for intestinal epithelial cell (IEC) homeostasis, and may thereby contribute to wound repair in colitis. However, whether cyclin Y has an essential function in IECs is unknown. We, therefore, investigated the epithelial injury response and mucosal regeneration in mice with conditional knock-out of Ccny in the intestinal epithelium. We observed that Ccny-deficient mice did not exhibit any differences in cell proliferation and disease activity compared to wild-type littermates in the dextran sulfate sodium (DSS) colitis model. Complementary in vitro experiments showed that loss of CCNY in model IECs did not affect Wnt signaling, cell proliferation, or autophagy. Additionally, we observed that expression of the cyclin-Y-associated cyclin-dependent kinase (CDK) 14 is exceedingly low specifically in IEC. Collectively, these results suggest that cyclin Y does not contribute to intestinal epithelial homeostasis, possibly due to low levels of specific CDKs in these cells. Thus, it is unlikely that CCNY mutations are causatively involved in IBD pathogenesis.