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Moving towards new therapeutic options

ECCO 2019

Pharmacological inhibition of autophagy was shown to exacerbate intestinal inflammation, fibrosis, and epithelial-mesenchymal transition (EMT) in a murine model [1]. In intestinal resections from Crohn’s disease patients, expression of autophagy markers correlated with expression of pro-fibrotic and pro-EMT genes.

Intestinal fibrosis was induced using the heterotopic transplant model. Segments of 1 cm colon from mice were subcutaneously transplanted into the neck of a recipient mice and collected after 7 days. Recipient mice were treated with a daily injection of autophagy inhibitor 3-MA (10 mg/kg). The results showed a significant increase in the expression of proinflammatory genes such as TNF-α, IL-1β, and IL-6. There was an increase in the expression of profibrotic genes such as Col1a1 and Vimentin. The expression of EMT genes such as Snail1 was significantly increased. Autophagy inhibition by 3-MA was confirmed by western blot, showing an increase of p...

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