Hepatocyte growth factor reduces CXCL10 expression in keratinocytes

Mitsuhiro Hisadome; Tomokazu Ohnishi; Kyoko Kakimoto; Joji Kusuyama; Kenjiro Bandow; Takuro Kanekura; Tetsuya Matsuguchi

doi:10.1002/1873-3468.12452

Hepatocyte growth factor reduces CXCL10 expression in keratinocytes

Mitsuhiro Hisadome, Tomokazu Ohnishi, Kyoko Kakimoto, Joji Kusuyama, Kenjiro Bandow, Takuro Kanekura, Tetsuya Matsuguchi

Creative Interdisciplinary Research Division

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Keratinocytes secrete vascular endothelial growth factor (VEGF) and angioregulatory chemokines during cutaneous wound healing. Hepatocyte growth factor (HGF) promotes skin re-epithelialization by increasing VEGF expression in keratinocytes. Here, we investigated the regulatory roles of HGF in the expression of genes encoding angiogenic and angiostatic chemokines in keratinocytes and found that HGF specifically inhibits mRNA expression of the angiostatic chemokine CXCL10 in both mouse primary keratinocytes and in the human keratinocyte cell line HaCaT through the MEK/ERK cascade. Furthermore, HGF inhibited tumor necrosis factor-α-induced CXCL10 expression at both mRNA and protein levels in HaCaT cells. Thus, HGF may orchestrate angiogenesis in wounded skin by modulating both VEGF and CXCL10 expression in keratinocytes.

Original language	English
Pages (from-to)	3595-3605
Number of pages	11
Journal	FEBS Letters
Volume	590
Issue number	20
DOIs	https://doi.org/10.1002/1873-3468.12452
Publication status	Published - 2016 Oct 1

Keywords

chemokines
tumor necrosis factor-α
vascular endothelial growth factor
wound healing

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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title = "Hepatocyte growth factor reduces CXCL10 expression in keratinocytes",

abstract = "Keratinocytes secrete vascular endothelial growth factor (VEGF) and angioregulatory chemokines during cutaneous wound healing. Hepatocyte growth factor (HGF) promotes skin re-epithelialization by increasing VEGF expression in keratinocytes. Here, we investigated the regulatory roles of HGF in the expression of genes encoding angiogenic and angiostatic chemokines in keratinocytes and found that HGF specifically inhibits mRNA expression of the angiostatic chemokine CXCL10 in both mouse primary keratinocytes and in the human keratinocyte cell line HaCaT through the MEK/ERK cascade. Furthermore, HGF inhibited tumor necrosis factor-α-induced CXCL10 expression at both mRNA and protein levels in HaCaT cells. Thus, HGF may orchestrate angiogenesis in wounded skin by modulating both VEGF and CXCL10 expression in keratinocytes.",

keywords = "chemokines, tumor necrosis factor-α, vascular endothelial growth factor, wound healing",

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AU - Hisadome, Mitsuhiro

AU - Ohnishi, Tomokazu

AU - Kakimoto, Kyoko

AU - Kusuyama, Joji

AU - Bandow, Kenjiro

AU - Kanekura, Takuro

AU - Matsuguchi, Tetsuya

PY - 2016/10/1

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N2 - Keratinocytes secrete vascular endothelial growth factor (VEGF) and angioregulatory chemokines during cutaneous wound healing. Hepatocyte growth factor (HGF) promotes skin re-epithelialization by increasing VEGF expression in keratinocytes. Here, we investigated the regulatory roles of HGF in the expression of genes encoding angiogenic and angiostatic chemokines in keratinocytes and found that HGF specifically inhibits mRNA expression of the angiostatic chemokine CXCL10 in both mouse primary keratinocytes and in the human keratinocyte cell line HaCaT through the MEK/ERK cascade. Furthermore, HGF inhibited tumor necrosis factor-α-induced CXCL10 expression at both mRNA and protein levels in HaCaT cells. Thus, HGF may orchestrate angiogenesis in wounded skin by modulating both VEGF and CXCL10 expression in keratinocytes.

AB - Keratinocytes secrete vascular endothelial growth factor (VEGF) and angioregulatory chemokines during cutaneous wound healing. Hepatocyte growth factor (HGF) promotes skin re-epithelialization by increasing VEGF expression in keratinocytes. Here, we investigated the regulatory roles of HGF in the expression of genes encoding angiogenic and angiostatic chemokines in keratinocytes and found that HGF specifically inhibits mRNA expression of the angiostatic chemokine CXCL10 in both mouse primary keratinocytes and in the human keratinocyte cell line HaCaT through the MEK/ERK cascade. Furthermore, HGF inhibited tumor necrosis factor-α-induced CXCL10 expression at both mRNA and protein levels in HaCaT cells. Thus, HGF may orchestrate angiogenesis in wounded skin by modulating both VEGF and CXCL10 expression in keratinocytes.

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