Induction of hepatocyte growth factor expression by maleic acid in human fibroblasts through MAPK activation

Motoki, Takayuki; Sugiura, Yoshimi; Matsumoto, Yohsuke; Tsuji, Toshiya; Kubota, Satoshi; Takigawa, Masaharu; Gohda, Eiichi

doi:10.1002/jcb.21724

Cited by 7 publications

(4 citation statements)

References 45 publications

(41 reference statements)

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“…The MEK/ERK1/2 pathway phosphorylates the transcription factor cAMP response element binding protein (CREB), which translocates into the nucleus and induces the transcription of BDNF and IGF-1 [ 55 , 56 , 57 , 58 ]. Recent studies have demonstrated that AKT and ERK1/2 also stimulate VEGF expression via HIF-1α activation [ 59 ] and that HGF production is upregulated by the RhoA-PI3K/Akt-MEK/ERK1/2 signaling axis [ 60 , 61 ]. Alongside these findings, the expression of neurotrophic and growth factors such as BDNF, VEGF, IGF-1, and HGF was increased in ETH-MSCs ( Figure S3 ).…”

Section: Discussionmentioning

confidence: 99%

Ethionamide Preconditioning Enhances the Proliferation and Migration of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells

Lee

Myeong

Son

et al. 2020

IJMS

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Mesenchymal stem cells (MSCs) are a useful source for cell-based therapy of a variety of immune-mediated diseases, including neurodegenerative disorders. However, poor migration ability and survival rate of MSCs after brain transplantation hinder the therapeutic effects in the disease microenvironment. Therefore, we attempted to use a preconditioning strategy with pharmacological agents to improve the cell proliferation and migration of MSCs. In this study, we identified ethionamide via the screening of a drug library, which enhanced the proliferation of MSCs. Preconditioning with ethionamide promoted the proliferation of Wharton’s jelly-derived MSCs (WJ-MSCs) by activating phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)1/2 signaling. Preconditioning with ethionamide also enhanced the migration ability of MSCs by upregulating expression of genes associated with migration, such as C-X-C motif chemokine receptor 4 (CXCR4) and C-X-C motif chemokine ligand 12 (CXCL12). Furthermore, preconditioning with ethionamide stimulated the secretion of paracrine factors, including neurotrophic and growth factors in MSCs. Compared to naïve MSCs, ethionamide-preconditioned MSCs (ETH-MSCs) were found to survive longer in the brain after transplantation. These results suggested that enhancing the biological process of MSCs induced by ethionamide preconditioning presents itself as a promising strategy for enhancing the effectiveness of MSCs-based therapies.

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Section: Discussionmentioning

confidence: 99%

Ethionamide Preconditioning Enhances the Proliferation and Migration of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells

Lee

Myeong

Son

et al. 2020

IJMS

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“…HGF gene transcription can be induced via several different intracellular signaling pathways, including MAPK and PI3K/Akt signaling pathways. In human fibroblasts, HGF expression induced by maleic acid requires activation of ERK and JNK, but not p38 MAPK [Motoki et al, 2008], whereas inflammatory cytokine IL‐1beta and IFN‐gamma‐induced HGF production in human fibroblasts requires activation of ERK and p38 MAPK but not of JNK [Takami et al, 2005]. In contrast, HGF production of human MSCs stimulated by LPS, or hypoxia depends on p38 MAPK activation but does not depend on increased ERK or JNK phosphorylation [Crisostomo et al, 2008].…”

Section: Discussionmentioning

confidence: 99%

Mechanism of TNF‐α‐induced migration and hepatocyte growth factor production in human mesenchymal stem cells

Zhang

Wang

Zhou

et al. 2010

J of Cellular Biochemistry

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Accumulating evidence suggests that mesenchymal stem cells (MSCs) may decrease destructive inflammation and reduce tissue loss. Tumor necrosis factor-α (TNF-α) plays a central role in induction of proinflammatory signaling and paradoxically activates intracellular anti-inflammatory survival pathways. In this study, we investigated whether TNF-α could induce a chemotactic effect on human MSCs and stimulate their production of anti-inflammatory factors in vitro, as well as determined mechanisms that mediated this effect. Migration assays demonstrated that TNF-α had a chemotactic effect on MSCs. TNF-α increased both hepatocyte growth factor (HGF) mRNA expression in MSCs and HGF secretion in conditioned medium. These effects were dependent on the p38 MAPK and PI3K/Akt, but not JNK and ERK signaling pathways. Furthermore, these effects were inhibited by a specific neutralizing antibody to TNF receptor II, but not TNF receptor I. We conclude that TNF-α can enhance human MSCs migration and stimulate their production of HGF. These effects are mediated via a specific TNF receptor and signaling pathways.

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“…Various stimulants induce HGF mRNA expression through MAPK activation [15,16]. Furthermore, gene expression of an angiogenic factor, cysteine-rich protein 61, was induced through RhoA and the p38 MAPK pathway in smooth muscle cells [19].…”

Section: Activation Of Mapks Up-regulates Apoptotic Cell-induced Hgf mentioning

confidence: 99%

RhoA-mediated signaling up-regulates hepatocyte growth factor gene and protein expression in response to apoptotic cells

Park

Choi²,

Cho³

et al. 2010

Journal of Leukocyte Biology

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Clearance of apoptotic cells by macrophages induces HGF secretion. We examined the regulatory mechanisms of HGF mRNA and protein expression in macrophages upon exposure to apoptotic cells. The interaction of RAW 264.7 macrophages with apoptotic Jurkat cells, but not with viable cells, resulted in expression of HGF mRNA and protein. Exposure of RAW 264.7 cells to apoptotic cells induced activation of RhoA, the PI3K/Akt pathway, and MAPKs, including p38 MAPK, ERK, and JNK. Down-regulation of the RhoA/Rho kinase pathway by pharmacological inhibitors or a RhoA-specific siRNA suppressed HGF mRNA and protein expression by macrophages in response to apoptotic cells through the phosphorylation of Akt and the MAPKs. Inhibition of PI3K decreased phosphorylation of Akt and the MAPKs. Inhibition of JNK, but not p38 MAPK and ERK, reduced Akt phosphorylation. The pharmacological inhibitor of PI3K and the MAPKs blocked HGF mRNA and protein expression. Other types of apoptotic cells, such as HeLa cells and murine thymocytes, could also induce HGF mRNA through the RhoA-dependent pathway. Likely, the RhoA-dependent signaling pathway was required for HGF mRNA induction in primary cells of peritoneal macrophages in response to apoptotic cells. An HGFR-blocking antibody did not alter apoptotic cell-induced activation of RhoA, Akt, and the MAPKs, as well as HGF production. Overall, the data provide evidence that activation of the RhoA/Rho kinase pathway up-regulates transcriptional HGF production in response to apoptotic cells.

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Induction of hepatocyte growth factor expression by maleic acid in human fibroblasts through MAPK activation

Cited by 7 publications

References 45 publications

Ethionamide Preconditioning Enhances the Proliferation and Migration of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells

Ethionamide Preconditioning Enhances the Proliferation and Migration of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells

Mechanism of TNF‐α‐induced migration and hepatocyte growth factor production in human mesenchymal stem cells

RhoA-mediated signaling up-regulates hepatocyte growth factor gene and protein expression in response to apoptotic cells

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