Insulin-like growth factor-II regulates the expression of vascular endothelial growth factor by the human keratinocyte cell line HaCaT

Yoo Wook Kwon, Kyung Sool Kwon, Hyo Eun Moon, Jeong Ae Park, Kyu Sil Choi, You Sun Kim, Ho Sun Jang, Chang Keun Oh, You Mie Lee, Young-Guen Kwon, Yun Sil Lee, Kyu Won Kim

Research output: Contribution to journalArticle

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Abstract

Psoriasis is a chronic, relapsing skin disease characterized by enhanced angiogenesis. The pathogenetic process resulting in hypervascularity remains to be further investigated. It has been reported that a potent angiogenic factor, vascular endothelial growth factor (VEGF) is overexpressed in psoriatic epidermis and that the level of insulin-like growth factor II (IGF-II) is significantly elevated in the tissue fluid and serum of the psoriatic lesion. We considered the possibility that IGF-II might function as a paracrine inducer of VEGF. Here, we demonstrated that exposure of HaCaT keratinocytes to IGF-II induced both mRNA and protein expression of VEGF through the MAP kinase (extracellular signal-regulated kinase (ERK2) pathway. Particularly, we determined that phosphorylation of ERK2 but not p38 and JNK1/2 was activated by IGF-II in a time-dependent manner. Additionally, we found that IGF-II treatment induced the expression of MDM2 through the MAP kinase pathway. Moreover, the increase of MDM2 resulted in decreased levels of p53 followed by increased expression of HIF-1α and VEGF. Taken together, these results suggest that IGF-II enhances the expression of VEGF in HaCaT cells by increasing HIF-1α levels.

Original languageEnglish
Pages (from-to)152-158
Number of pages7
JournalJournal of Investigative Dermatology
Volume123
Issue number1
DOIs
Publication statusPublished - 2004 Jan 1

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Insulin-Like Growth Factor II
Keratinocytes
Vascular Endothelial Growth Factor A
Cells
Cell Line
Phosphotransferases
Phosphorylation
Angiogenesis Inducing Agents
Extracellular Signal-Regulated MAP Kinases
Psoriasis
Skin Diseases
Epidermis
human VEGFA protein
Skin
Tissue
Messenger RNA
Fluids
Serum
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Kwon, Yoo Wook ; Kwon, Kyung Sool ; Moon, Hyo Eun ; Park, Jeong Ae ; Choi, Kyu Sil ; Kim, You Sun ; Jang, Ho Sun ; Oh, Chang Keun ; Lee, You Mie ; Kwon, Young-Guen ; Lee, Yun Sil ; Kim, Kyu Won. / Insulin-like growth factor-II regulates the expression of vascular endothelial growth factor by the human keratinocyte cell line HaCaT. In: Journal of Investigative Dermatology. 2004 ; Vol. 123, No. 1. pp. 152-158.
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abstract = "Psoriasis is a chronic, relapsing skin disease characterized by enhanced angiogenesis. The pathogenetic process resulting in hypervascularity remains to be further investigated. It has been reported that a potent angiogenic factor, vascular endothelial growth factor (VEGF) is overexpressed in psoriatic epidermis and that the level of insulin-like growth factor II (IGF-II) is significantly elevated in the tissue fluid and serum of the psoriatic lesion. We considered the possibility that IGF-II might function as a paracrine inducer of VEGF. Here, we demonstrated that exposure of HaCaT keratinocytes to IGF-II induced both mRNA and protein expression of VEGF through the MAP kinase (extracellular signal-regulated kinase (ERK2) pathway. Particularly, we determined that phosphorylation of ERK2 but not p38 and JNK1/2 was activated by IGF-II in a time-dependent manner. Additionally, we found that IGF-II treatment induced the expression of MDM2 through the MAP kinase pathway. Moreover, the increase of MDM2 resulted in decreased levels of p53 followed by increased expression of HIF-1α and VEGF. Taken together, these results suggest that IGF-II enhances the expression of VEGF in HaCaT cells by increasing HIF-1α levels.",
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Insulin-like growth factor-II regulates the expression of vascular endothelial growth factor by the human keratinocyte cell line HaCaT. / Kwon, Yoo Wook; Kwon, Kyung Sool; Moon, Hyo Eun; Park, Jeong Ae; Choi, Kyu Sil; Kim, You Sun; Jang, Ho Sun; Oh, Chang Keun; Lee, You Mie; Kwon, Young-Guen; Lee, Yun Sil; Kim, Kyu Won.

In: Journal of Investigative Dermatology, Vol. 123, No. 1, 01.01.2004, p. 152-158.

Research output: Contribution to journalArticle

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