Caveolar communication with xenobiotic-stalled ribosomes compromises gut barrier integrity.
Seong-Hwan ParkJuil KimYuseok MoonPublished in: Communications biology (2020)
In response to internal and external insults, the intestinal lining undergoes various types of epithelial adaptation or pathologic distress via stress-responsive eIF2α kinase signaling and subsequent cellular reprogramming. As a vital platform for growth factor-linked adaptive signaling, caveolae were evaluated for epithelial modulation of the insulted gut. Patients under ulcerative insult displayed enhanced expression of caveolin-1, the main structural component of caveolae, which was positively associated with expression of protein kinase R (PKR), the ribosomal stress-responsive eIF2α kinase. PKR-linked biological responses were simulated in experimental gut models of ribosome-inactivating stress using mice and Caenorhabditis elegans. Caveolar activation counteracted the expression of wound-protective epidermal growth factor receptor (EGFR) and its target genes, such as chemokines that were pivotal for epithelial integrity in the ribosome-inactivated gut. Mechanistic findings regarding ribosomal inactivation-associated disorders in the gut barrier provide crucial molecular evidence for detrimental caveolar actions against EGFR-mediated epithelial protection in patients with IBD.
Keyphrases
- epidermal growth factor receptor
- tyrosine kinase
- poor prognosis
- growth factor
- protein kinase
- small cell lung cancer
- advanced non small cell lung cancer
- end stage renal disease
- chronic kidney disease
- binding protein
- newly diagnosed
- neoadjuvant chemotherapy
- long non coding rna
- squamous cell carcinoma
- type diabetes
- genome wide
- stress induced
- high throughput
- transcription factor
- heat stress
- high fat diet induced
- rectal cancer
- insulin resistance
- locally advanced