期刊
JOURNAL OF CELL SCIENCE
卷 121, 期 15, 页码 2493-2502出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.025528
关键词
basement membrane; small intestine; intestinal epithelial cell; Lutheran (Bcam); p27Kip1 (Cdkn1b)
类别
资金
- NCRR NIH HHS [C06 RR015502, C06RR015502] Funding Source: Medline
- NHLBI NIH HHS [P01HL029594, P01 HL029594] Funding Source: Medline
- NIDCD NIH HHS [P30DC004665, P30 DC004665] Funding Source: Medline
- NIDDK NIH HHS [P30 DK052574, R01 DK064687-02, R01 DK064687-03, P30DK052574, P30 DK079333, R01 DK064687, R01 DK064687-04, R01DK064687, P30DK079333] Funding Source: Medline
- NIGMS NIH HHS [R01 GM060432-07, R01 GM060432, R01 GM060432-05, R01 GM060432-06, R01GM060432, R01 GM060432-03, R01 GM060432-04] Funding Source: Medline
The mammalian intestine displays two distinct patterns of mucosal organization. The small intestine contains mucosal epithelial invaginations ( the crypts of Lieberkuhn) that are continuous with evaginations ( villi) into the lumen. The colon also contains crypts of Lieberkuhn, 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 a5 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 a5 has a crucial role in establishing and maintaining the specific mucosal pattern of the mouse small intestine.
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