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    11 views9 pages

    Scatter Factor Modulates Intestinal Epithelial Cell Proliferation and Migration PDF

    Uploaded by

    Martina Alice Palumbo

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
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    Vol. 202, No. 2, 1994 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS July 29, 1994 Pages 701-709 HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR MODULATES INTESTINAL EPITHELIAL CELL PROLIFERATION AND MIGRATION ‘Axel U. Dignass, Kathryn Lynch-Devaney, and Daniel K. Podolsky? Gastrointestinal Unit, Department of Medicine, and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA. Received June 9, 1994 SUMMARY: Various peptide growth factors have been found to regulate epithelial cell function within the mucosal epithelium of the gastrointestinal tract. In this study hepatocyte growth factor/scatter factor (HGF/SF) was found to stimulate intestinal epithelial cell proliferation: 2.5-fold in the non-transformed rat small intestinal epithelial cell line IEC- 6 and 1.9-fold in the human colon cancer-derived HT-29 cell line. In addition, HGF/SF enhanced epithelial cell restitution, the initial step involved in gastrointestinal wound healing, in an in vitro model. Migration of IEC-6 in wounded monolayers was enhanced up to 7- fold. Enhancement of restitution by HGF could be completely abrogated by addition of immunoneutralizing anti-TGF81, indicating that this process is mediated through a TGFA- dependent pathway. These findings suggest that HGF exerts functional effects on intestinal epithelial cell populations and may play a role in the morphogenesis of the gastrointestinal tract and its remodeling following injury. © 129 scadem Hepatocyte growth factor (HGF) was first described as a hepatotrophic factor present in the serum of rats after partial hepateciomy (1,2) and in rat platelets (3). Scatter factor (SF) was characterized originally as a fibroblast and smooth muscle cell-derived growth factor which stimulated the motility of epithelial cells (4-6). More recent studies have revealed that scatter factor and HGF are identical peptides with identical bioactivities (7-9). To whom correspondence should be addressed at Gastrointestinal Unit, GRJ-719, ‘Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114. Fax: (617) 726- 3673. ABBREVIATIONS: DMEM, Dulbecco's modified Eagle medium; EGF, epidermal growth factor; FCS, fetal calf serum; FGF, fibroblast growth factor; IFN~y, interferon 7; IL-18, interleukin 18; KGF, keratinocyte growth factor, Mv1Lu, mink lung epithelial cells; TGF, transforming growth factor; HGF, hepatocyte growth factor; SP, scatter factor. 0006.291X/94 $5.00 Copyright © 1994 by Academic Press, Inc TOL Allrights of reproduction in any form reserved. Vol. 202, No. 2, 1984 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Both hepatocyte growth factor and scatter factor have now been recognized to be the natural ligands of the tyrosine kinase receptor encoded by the c-met protooncogene (9-10). Recent studies have demonstrated the expression of both me/HGF receptor mRNA and protein in a broad range of tissues, including stomach, small intestine, and colon (11). Little information is available on the biological activities of HGF in the small and large intestine, but it is plausible that HGF may play a role in the morphogenesis of the gastrointestinal tract and its remodeling following injury (12). Previous studies in our laboratory and elsewhere (13-20) have demonstrated the ability of a variety of growth factors and cytokines to modulate epithetial cell proliferation and

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