Dataset Information

Smooth muscle-specific MMP17 (MT4-MMP) defines the intestinal ECM niche

ABSTRACT: 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 may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Smooth Muscle

SUBMITTER: Mirjam Damen

LAB HEAD: Menno Oudhoff

PROVIDER: PXD020561 | Pride | 2021-11-02

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20191003_OR14_Ag2_Damen101_SA_MA_KO1.raw	Raw
	20191003_OR14_Ag2_Damen101_SA_MA_KO2.raw	Raw
	20191003_OR14_Ag2_Damen101_SA_MA_KO3.raw	Raw
	20191003_OR14_Ag2_Damen101_SA_MA_WT1.raw	Raw
	20191003_OR14_Ag2_Damen101_SA_MA_WT2.raw	Raw

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Publications

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

Martín-Alonso Mara M Iqbal Sharif S Vornewald Pia M PM Lindholm Håvard T HT Damen Mirjam J MJ Martínez Fernando F Hoel Sigrid S Díez-Sánchez Alberto A Altelaar Maarten M Katajisto Pekka P Arroyo Alicia G AG Oudhoff Menno J MJ

Nature communications 20211118 1

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 ...[more]

PMID: 34795242

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