title: Laminin alpha 5 influences the architecture of the mouse small intestine mucosa.
abstract: The mammalian intestine displays two distinct patterns of mucosal organization. The small intestine contains mucosal epithelial invaginations (the crypts of Lieberkühn) that are continuous with evaginations (villi) into the lumen. The colon also contains crypts of Lieberkühn, but its epithelial surface is lined by flat surface cuffs. The epithelial cells of both organs communicate with the underlying mesenchyme through a basement membrane that is composed of a variety of extracellular matrix proteins, including members of the laminin family. The basement membranes of the small intestine and colon contain distinct laminin subtypes; notably, the villus basement membrane is rich in laminin alpha 5. Here, we show that the diminution of laminin alpha 5 in a mouse model led to a compensatory deposition of colonic laminins, which resulted in a transformation from a small intestinal to a colonic mucosal architecture. The alteration in mucosal architecture was associated with reduced levels of nuclear p27Kip1 - a cell-cycle regulator - and altered intestinal epithelial cell proliferation, migration and differentiation. Our results suggest that laminin alpha 5 has a crucial role in establishing and maintaining the specific mucosal pattern of the mouse small intestine.
authors.affiliation: Department of Internal Medicine/Renal Division, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Zhen X
authors.initials: ZX
authors.lastname: Mahoney
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miner
mesh_terms: D000818:Animals; D017209:Apoptosis; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D019076:Transgenes
chemical_list: C477645:Bcam protein, mouse; C493961:Cdkn1b protein, mouse; D015815:Cell Adhesion Molecules; D007797:Laminin; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins; C097043:laminin alpha5; D050760:Cyclin-Dependent Kinase Inhibitor p27