Novel Function of Prostaglandins as Inducers of Gene Expression of HGF and Putative Mediators of Tissue Regeneration
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概要
- 論文の詳細を見る
Prostaglandins (PGs) are multi-potent mediators for local tissue homeostasis and inflammatory reactions. Addition of PGs to cultures of human skin fibroblasts led to a marked induction of the production of hepatocyte growth factor (HGF). PGE1 and PGI2 analogues were the most potent in stimulating HGF production by over 50-fold; PGE2 and PGD2 were less potent. Western immunoblotting of conditioned medium from skin fibroblasts indicated that both PGE1, PGE2, and PGI2 analogues specifically induce synthesis of HGF with a Mr of 85, 000, but not smaller variant of HGF with a Mr of 28, 000. Consistent with the induction of HGF production, steady-state expression of HGF mRNA in fibroblasts was strongly induced by PGE1 and PGI2 analogues, but slightly by PGE2 and PGD2, thereby indicating that PGs induce HGF production through transcriptional activation of the HGF gene. PGE1, PGE2, PGI2 analogue also stimulated HGF production in MRC-5 human embryonic lung fibroblasts and vascular smooth muscle cells. As dibutyryl cyclicAMP (dbcAMP) and tetradecanoylphorbol 13-acetate (TPA), but not Ca2+-ionophore A 23187 stimulated HGF production in skin fibroblasts, activation of protein kinase-A and protein kinase-C may be coupled to the stimulation of HGF production. Simultaneous addition of PGE1 and TPA or dbcAMP and TPA led to a synergistic enhancement of HGF production, whereas the simultaneous addition of PGE1 and dbcAMP failed to additively enhance HGF production. This means that GS-coupled PG receptors may be responsible for the induction of HGF. HGF, a ligand for the c-met protooncogene product is a potent organotrophic factor which elicits mitogenic, motogenic, and morphogenic activities for regeneration of tissues and organs. These results indicate that PGE1 and PGI2 are strong transcriptional inducers for HGF gene expression and these PGs, rapidly synthesized following tissue injuries and diseases, may have a role as important mediators to induce HGF expression.
- 社団法人 日本生化学会の論文
著者
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Okazaki Hiroko
Division Of Biochemistry Biomedical Research Center Osaka University Medical School
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Matsumoto Kunio
Division Of Bichemistry Biomedical Research Center Osaka University Medical School
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Nakamura Toshikazu
Division Of Bichemistry Biomedical Research Center Osaka University Medical School
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