Basic—Alimentary TractLoss of Indian Hedgehog Activates Multiple Aspects of a Wound Healing Response in the Mouse Intestine
Section snippets
Materials and Methods
See the Supplementary Materials and Methods section for details.
Loss of Ihh Signaling in Adult β-Naphthoflavone–Injected Cyp1a1Cre-Ihhfl/fl Mice
We examined expression of Ihh messenger RNA (mRNA) (Figure 1A) and protein (Figure 1B) in the small intestine of the mouse. Both Ihh protein and mRNA were expressed exclusively by the differentiated epithelial cells on the villi. To examine the role of Ihh signaling in the adult small intestinal mucosa we injected adult Cyp1a1-Ihhfl/fl mice and Ihhfl/fl control mice with β-naphthoflavone. This resulted in substantially reduced expression of Ihh protein (Figure1B, right panel). Quantitative
Discussion
We find that loss of Ihh results in an epithelial response that is characteristic of epithelial wound repair and is associated with loss of both Bmp and Activin signaling in the epithelial cells. In addition to the epithelial remodeling we observed substantial recruitment of macrophages and fibroblasts, 2 critical mesenchymal cell types involved in wound repair, into the villus core. Unresolved loss of Ihh ultimately results in loss of smooth muscle cells, the establishment of a pericryptal
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Conflicts of interest The authors disclose no conflicts.
Funding The research leading to these results has received funding from the European Research Council under the European Community's Seventh Framework Program (FP7/2007-2013)/European Research Council grant agreement number 241344 and by a grant from the Dutch Digestive Foundation. Generation of floxed Ihh mice was funded by the National Institutes of Health (AR050560 to B.L.).