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Induction of hepatocyte growth factor expression by maleic acid in human fibroblasts through MAPK activation
Author(s) -
Motoki Takahiro,
Sugiura Yoshihiro,
Matsumoto Yohsuke,
Tsuji Tomoe,
Kubota Satoshi,
Takigawa Masaharu,
Gohda Eiichi
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21724
Subject(s) - maleic acid , hepatocyte growth factor , mapk/erk pathway , cycloheximide , downregulation and upregulation , kinase , p38 mitogen activated protein kinases , protein kinase a , chemistry , signal transduction , protein kinase c , microbiology and biotechnology , biology , biochemistry , protein biosynthesis , receptor , organic chemistry , copolymer , gene , polymer
Carboxylic acids have various biological activities and play critical roles in cellular metabolic pathways such as the tricarboxylic acid (TCA) cycle. It has been shown that some carboxylic acids induce cell proliferation and production of cytokines or growth factors. However, there have been no reports on effects of carboxylic acids on hepatocyte growth factor (HGF) expression. In this study, we found that only maleic acid among various carboxylic acids examined markedly induced HGF production from human dermal fibroblasts. Maleic acid also induced HGF production from human lung fibroblasts and neuroblastoma cells. The stimulatory effect was accompanied by upregulation of HGF gene expression. Increase in phosphorylation of extracellular signal‐regulated protein kinase (ERK) and c‐Jun N‐terminal kinase (JNK) but not in phosphorylation of p38 was observed from 6 h and up to 24 h after maleic acid addition. The ERK kinase inhibitor PD98059 and the JNK inhibitor SP600125 potently inhibited maleic acid‐induced HGF production, while the p38 inhibitor SB203580 did not significantly inhibit the production. The protein synthesis inhibitor cycloheximide completely inhibited upregulation of HGF mRNA induced by maleic acid but superinduced HGF mRNA expression upregulated by 12‐ O ‐tetradecanoylphorbol 13‐acetate (TPA). These results suggest that maleic acid indirectly induced HGF expression from human dermal fibroblasts through activation of ERK and JNK and that de novo protein synthesis is required for maleic acid‐induced upregulation of HGF mRNA. J. Cell. Biochem. 104: 1465–1476, 2008. © 2008 Wiley‐Liss, Inc.