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.
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Hisadome
authors.affiliation: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ohnishi
authors.affiliation: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kakimoto
authors.affiliation: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Kusuyama
authors.affiliation: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Bandow
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
authors.affiliation: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Japan. tmatsugu@dent.kagoshima-u.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuguchi
mesh_terms: D000818:Animals; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000235:genetics*; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C066855:HGF protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor
keywords: chemokines; tumor necrosis factor-α; vascular endothelial growth factor; wound healing