@article{a15e65605ecd407b9aa5b1ed8bb53dc4,
title = "Extracellular Matrix Modulates Enterocyte Growth via Downregulation of c-jun But Is Independent of p21 and p27 Expression",
abstract = "Regulation of the intestinal crypt-villus axis is multifactorial and involves growth factors and extracellular matrix composition. Laminin, a component of the enterocyte basement membrane, induces enterocyte differentiation and inhibits proliferation. To investigate the mechanism of this observation, we examined the expression of cell cycle modulators in enterocytes cultured on laminin. IEC-6 enterocytes were cultured on collagen I or laminin for 24 hours in media with serum followed by 48 hours of culture in serum-free media. Cells were then stimulated with epidermal growth factor, and RNA and protein were extracted before and up to 18 hours after stimulation. c-jun mRNA expression and p21 and p27 protein expression were analyzed. Expression of c-jun was inhibited in cells grown on laminin as compared to collagen I. Expression of p21 and p27 was no different between cells grown on laminin or collagen I. The mechanism of enterocyte growth inhibition mediated by laminin involves downregulation of c-jun expression. In contrast, p21 and p27 levels were unaffected by extracellular matrix indicating that the changes in expression of these cyclin-dependent kinase inhibitors do not contribute to the effect of laminin on enterocyte proliferation.",
keywords = "Basement membrane, Cyclin-dependent kinase inhibitor, Enterocyte, Growth, Oncogene",
author = "Wolpert, {Seth I.} and Lally, {Kathleen M.} and Ji Li and Wang, {Jian Ying} and {Lee Bass}, Barbara",
note = "Funding Information: The small bowel epithelium undergoes rapid turnover. Intestinal crypt cells proliferate to yield the terminally differentiated cells of the villus tip, a process that is completed every 3 to 5 days. It is the cells along the villus that carry out the absorptive function of the bowel. The regulatory mechanisms responsible for maintaining the balance between these populations of enterocytes are poorly understood and likely multifactorial. Peptide growth factors are operative in this process as epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) have been shown to stimulate enterocyte proliferation, I-3 whereas transforming growth factor beta (TGF-13) inhibits growth and stimulates differentiation. 4 The basement membrane of the intestinal epithelium has also been shown to be active in enterocyte phenotype regulation. The extracellular matrix is composed of a number of proteins and proteoglycans including laminin, collagen IV,, fibronectin, entactin, and heparan sulfate. Although laminin is present throughout the crypt-villus axis, 5 isoforms of laminin have been found to predominate in either the crypts or villus tips. 6 Enterocytes cultured on laminin exhibit a differentiated phenotype as assessed by ultrastructural changes including microvilli, increased mitochondria, and rough endoplasmic reticulum, as well as expression of brush-border enzymes. 7,s Although these features of differentiation induced by laminin have been well described, the effect of matrix on enterocyte growth is just beginning to be explored. We have previously demonstrated that laminin inhibits EGF-and IGF-I-induced entero- From the Department of Surgery,U niversityo f Maryland, and the BaltimoreV A Medical Center, Baltimore, Md. Supported by a merit reviewg rant from the Department of Veterans AffairsR esearch Service (B.L.B.). Presented at the Thirty-Ninth AnnualM eeting of The Societyf or Surgeryo f the AlimentaryT ract, New Orleans, La., May 17-20, 1998. Reprint requests: Dr. Barbara Lee Bass, Surgical Care Center, Baltimore VA Medical Center, 10 North Greene St., Baltimore, MD 21201.",
year = "1999",
doi = "10.1016/S1091-255X(99)80074-2",
language = "English (US)",
volume = "3",
pages = "319--324",
journal = "Journal of Gastrointestinal Surgery",
issn = "1091-255X",
publisher = "Springer New York",
number = "3",
}