Distraction Enterogenesis Induces Desert Hedgehog in the Lengthened Murine Colon.

Background: Distraction enterogenesis lengthens the intestine through applied mechanical stress. The Hedgehog pathway (Hh) is responsible for intestinal tract development and directing the multi-layer patterning of the intestinal lumen. This study investigates the alteration in the principal components of this pathway in spring-mediated colonic lengthening.

Methods: Samples from the murine cecal lengthening model were used to study Hh alteration during the cecal lengthening process. Primary components of this pathway were analyzed using RT-qPCR and immunostaining after 7 and 14 days of force application. The spring-mediated lengthened segments were compared to untreated control segments within each animal.

Results: The spring-treated segments showed a 50% increase in length. There was a significant increase in the expression of the Desert Hedgehog ligand as opposed to the Sonic Hedgehog and Indian Hedgehog ligands. Additionally, the downstream targets of the pathway, Gli1, Gli2, and Gli3, were significantly overexpressed. The highest alterations in these components occurred at the earlier time point, after 7 days.

Conclusions: These findings highlight the contribution of the conserved Hedgehog developmental pathway during mechanical force-induced cecal lengthening, primarily through the Desert Hedgehog ligand. These data suggest that the Desert Hedgehog pathway may serve as therapeutic targets for intestinal regeneration.