Receptor phenotype underlies differential response of hepatocytes and nonparenchymal cells to heparin-binding fibroblast growth factor type 1 (aFGF) and type 2 (bFGF) |
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Authors: | Mikio Kan Guo-Chen Yan Jianming Xu Mitsuru Nakahara Jinzhao Hou |
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Institution: | (1) W. Alton Jones Cell Science Center, Inc., Old Barn Road, 12946 Lake Placid, New York;(2) Present address: Department of Urology, School of Medicine, Hiroshima University, 1-2-3 Kasumi-cho Minami-ku, Hiroshima, Japan |
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Abstract: | Summary Heparin-binding fibroblast growth factors (HBGF) have been implicated in the regeneration of both parenchymal and nonparenchymal
cells of the liver. The response to and phenotype of hepatocyte receptors for HBGF-1 (acidic fibroblast growth factor) and
HBGF-2 (basic fibroblast growth factor) were compared to keratinocytes, fibroblasts, and endothelial cells. HBGF-1 stimulated
DNA synthesis in hepatocytes, keratinocytes, fibroblasts, and endothelial cells whereas activity of HBGF-2 was limited to
fibroblasts and endothelial cells. HBGF-2 antagonized the mitogenic activity of HBGF-1 for hepatocytes and keratinocytes.
Hepatocytes and keratinocytes exhibited both high- and low-affinity, nonmatrix receptor sites for HBGF-1, but only low-affinity
sites for HBGF-2. The mesenchymal cells displayed only high-affinity sites for both HBGF-1 and HBGF-2. Northern blot and immunochemical
analysis revealed that the expression of HBGF receptor genesbek andflg are partitioned between normal hepatocytes and nonparenchymal cells, respectively. Expression of epithelial cell-specific,
mesenchymal cell-derived HBGF-7 (keratinocyte growth factor) mRNA in regenerating liver tissue was undetectable relative to
HBGF-1. The results support a multifunctional role of HBGF-1 acting through different receptor phenotypes in hepatocyte and
nonparenchymal cells during liver regeneration. |
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Keywords: | liver regeneration compensatory growth signal transduction epithelial-stromal interactions |
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