caa a22 4500 39749405X CHVBK 20180308164516.0 cr unu---uuuuu 161202e199502 xx s 000 0 eng 10.1093/jb/117.2.458 doi (NATIONALLICENCE)oxford-10.1093/jb/117.2.458 Novel Function of Prostaglandins as Inducers of Gene Expression of HGF and Putative Mediators of Tissue Regeneration [Elektronische Daten] [Kunio Matsumoto, Hiroko Okazaki, Toshikazu Nakamura] 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 indicat ed 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 PGE and PGD 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 Ca A23187 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 PGE and TPA or dbcAMP and TPA led to a synergistic enhancement of HGF production, whereas the simultaneous addition of PGE and dbcAMP failed to additively enhance HGF production. This means that G3 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. © BY THE JOURNAL OF BIOCHEMISTRY Regular Papers nationallicence c-met nationallicence fibroblast nationallicence hepatocyte growth factor nationallicence liver regeneration nationallicence prostaglandin nationallicence Matsumoto Kunio Division of Biochemistry, Biomedical Research Center, Osaka University Medical School Suita, Osaka 565 aut Okazaki Hiroko Division of Biochemistry, Biomedical Research Center, Osaka University Medical School Suita, Osaka 565 aut Nakamura Toshikazu Division of Biochemistry, Biomedical Research Center, Osaka University Medical School Suita, Osaka 565 aut The Journal of Biochemistry Oxford University Press 117/2(1995-02), 458-464 0021-924X 117:2<458 1995 117 jbchem https://doi.org/10.1093/jb/117.2.458 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jb/117.2.458 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Matsumoto Kunio Division of Biochemistry, Biomedical Research Center, Osaka University Medical School Suita, Osaka 565 aut NATIONALLICENCE 700 1- Okazaki Hiroko Division of Biochemistry, Biomedical Research Center, Osaka University Medical School Suita, Osaka 565 aut NATIONALLICENCE 700 1- Nakamura Toshikazu Division of Biochemistry, Biomedical Research Center, Osaka University Medical School Suita, Osaka 565 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 117/2(1995-02), 458-464 0021-924X 117:2<458 1995 117 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford