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

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47 Citations (Scopus)

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 Jul

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Kwon, Y. W., Kwon, K. S., Moon, H. E., Park, J. A., Choi, K. S., Kim, Y. S., Jang, H. S., Oh, C. K., Lee, Y. M., Kwon, Y. G., Lee, Y. S., & Kim, K. W. (2004). Insulin-like growth factor-II regulates the expression of vascular endothelial growth factor by the human keratinocyte cell line HaCaT. Journal of Investigative Dermatology, 123(1), 152-158. https://doi.org/10.1111/j.0022-202X.2004.22735.x