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Keratinocyte growth factor–just another mitogen or the “holy grail” that regulates liver regeneration?
Author(s) -
Guha Chandan,
Chowdhury Jayanta Roy
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840220640
Subject(s) - holy grail , regeneration (biology) , liver regeneration , microbiology and biotechnology , keratinocyte growth factor , keratinocyte , epidermal growth factor , growth factor , mapk/erk pathway , biology , cancer research , immunology , medicine , kinase , in vitro , cell culture , genetics , computer science , receptor , world wide web
Keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF) family, was identified as a specific keratinocyte mitogen after isolation from a lung fibroblast line. Recently, recombinant (r)KGF was found to influence proliferation and differentiation patterns of multiple epithelial cell lineages within skin, lung, and the reproductive tract. In the present study, we designed experiments to identify additional target tissues, and focused on the rat gastrointestinal (GI) system, since a putative receptor, K‐ sam , was originally identified in a gastric carcinoma. Expression of KGF receptor and KGF mRNA was detected within the entire GI tract, suggesting the gut both synthesized and responded to KGF. Therefore, rKGF was administered to adult rats and was found to induce markedly increased proliferation of epithelial cells from the foregut to the colon, and of hepatocytes, one day after systemic treatment. Daily treatment resulted in the marked selective induction of mucin‐producing cell lineages throughout the GI tract in a dose‐dependent fashion. Other cell lineages were either unaffected (e.g., Paneth cells), or relatively decreased (e.g., parietal cells, enterocytes) in rKGF‐treated rats. The direct effect of rKGF was confirmed by demonstrating markedly increased carcinoembryonic antigen production in a human colon carcinoma cell line, LIM1899. Serum levels of albumin were specifically and significantly elevated after daily treatment. These results demonstrate rKGF can induce epithelial cell activation throughout the GI tract and liver. Further, endogenous KGF may be a normal paracrine mediator of growth within the gut. ( J. Clin. Invest . 1994. 94:1764–1777.) Key words: fibroblast growth factors carcinoembryonic antigen colon carcinoma gastric small intestine. (Reproduced from The Journal of Clinical Investigation, 1994, vol. 94, pp. 1764‐1777 by copyright permission of The Society for Clinical Investigation).