Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage

Smooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle cells may have. Here, we show that smooth muscle cells may be the dominant suppliers of BMP antagonists, which are niche factors essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the membrane-bound matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle cells, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we propose that MMP17 affects intestinal epithelial reprogramming after damage indirectly by cleaving diffusible factor(s) such as the matricellular protein PERIOSTIN. Together, we identify an important signaling axis that establishes a role for smooth muscle cells as modulators of intestinal epithelial regeneration and the intestinal stem cell niche. While the role of smooth muscle in peristalsis has been studied extensively, little is known about its other functions in the intestine. Here the authors identify MMP17, expressed by smooth muscle cells, as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.

Automated summary

Smooth muscle cells in the intestine may play a crucial role in supplying BMP antagonists, maintaining reparative and fetal-like features, and influencing intestinal epithelial regeneration through MMP17. This discovery establishes smooth muscle cells as modulators of intestinal epithelial regeneration and the stem cell niche.