Loss of Skiv2l triggers altered cell differentiation and compromises intestinal barrier integrity*

Presenter Information

John HargyFollow

Presentation Type

Poster Presentation

Mentor/Supervising Professor Name

Laing, Blake

Abstract (Description of Research)

Disruption of the intestinal epithelial barrier increases microbial exposure, triggering inflammation and exacerbating autoimmune disorders like inflammatory bowel disease (IBD). Current treatments focus on immune suppression, often leading to side effects. Tricho-Hepato-Enteric syndrome (THES), a rare early-onset IBD, results from mutations in SKIV2L or TTC37, both components of the RNA exosome. Using VillinCreER; Skiv2l^fl/fl mouse intestinal organoids, we show Skiv2l deletion induces ER stress, with elevated ER stress proteins by 48 hours and reduced organoid formation efficiency. These findings suggest Skiv2l maintains epithelial integrity via mRNA regulation and ER homeostasis, offering therapeutic insight beyond immune suppression.

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Loss of Skiv2l triggers altered cell differentiation and compromises intestinal barrier integrity*

Disruption of the intestinal epithelial barrier increases microbial exposure, triggering inflammation and exacerbating autoimmune disorders like inflammatory bowel disease (IBD). Current treatments focus on immune suppression, often leading to side effects. Tricho-Hepato-Enteric syndrome (THES), a rare early-onset IBD, results from mutations in SKIV2L or TTC37, both components of the RNA exosome. Using VillinCreER; Skiv2l^fl/fl mouse intestinal organoids, we show Skiv2l deletion induces ER stress, with elevated ER stress proteins by 48 hours and reduced organoid formation efficiency. These findings suggest Skiv2l maintains epithelial integrity via mRNA regulation and ER homeostasis, offering therapeutic insight beyond immune suppression.