Insulin-like growth factor-II regulates the 12-lipoxygenase gene expression and promotes cell proliferation in human keratinocytes via the extracellular regulatory kinase and phosphatidylinositol 3-kinase pathways.

Abstract

To study the relationship between insulin-like growth factor-II (IGF-II) and 12-lipoxygenase (12-LOX) that are upregulated in psoriasis, we monitored 12-lipoxygenase expression in the insulin-like growth factor-II treated human keratinocytes and explored the signaling pathways of 12-lipoxygenase expression. Insulin-like growth factor-II induced 12-lipoxygenase mRNA and protein levels in human keratinocytes through two major signal transduction pathways, namely, the extracellular signaling-regulated kinase (ERK)-mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. The IGF-II-induced upregulation of 12-lipoxygenase was attenuated by pretreating the cells with selective inhibitors or by overexpressing dominant-negative MEK. In addition, treatment of HaCaT cells with the 12-lipoxygenase metabolite 12 (S)-hydroxyeicosatetraenoic acid (12(S)-HETE) directly stimulated DNA synthesis and mitogenesis, and injection of insulin-like growth factor-II into the skin of hairless mice induced epidermal hyperplasia. These results suggest that insulin-like growth factor-II is involved in the pathogenesis of psoriasis as a paracrine inducer of 12-lipoxygenase.

• Authors: Hyun Yoo, Su-Jin Kim, Younghwa Kim, Hyangkyu Lee, Tae-Yoon Kim
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 39 Issue 6 Pg. 1248-59 ( 2007) ISSN: 1357-2725 [Print] Netherlands
• PMID: 17521953 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromones
• Flavonoids
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-fos
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
• Insulin-Like Growth Factor II
• Arachidonate 12-Lipoxygenase
• Extracellular Signal-Regulated MAP Kinases
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid (pharmacology)
• Animals
• Arachidonate 12-Lipoxygenase (genetics, metabolism)
• Blotting, Northern
• Blotting, Western
• Cell Line
• Cell Line, Transformed
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Flavonoids (pharmacology)
• Gene Expression (drug effects)
• Humans
• Insulin-Like Growth Factor II (pharmacology)
• Keratinocytes (cytology, drug effects, metabolism)
• Mice
• Mice, Hairless
• Morpholines (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-fos (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Skin (drug effects, metabolism)