Calcitonin gene-related peptide regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes by activation of ERK1/2 MAPK.

Abstract

Psoriasis is a chronic disease characterized by abnormal epidermal proliferation, inflammation and 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 calcitonin gene-related peptide (CGRP) is elevated in psoriasis lesions and CGRP-containing neuropeptide nerve fibers are denser in the psoriatic epidermis. We hypothesized that CGRP might regulate the expression of VEGF by human keratinocytes. VEGF expression in the CGRP-treated human keratinocytes was investigated and the CGRP signaling pathways were examined with respect to VEGF expression. The mRNA and protein levels of VEGF by CGRP were increased in a concentration-dependent manner. However, this increase was abrogated by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor PD98059. The CGRP-mediated VEGF induction was also effectively inhibited by a pretreatment with the CGRP receptor antagonist CGRP 8-37. In addition, CGRP treatment induced rapid phosphorylation of ERK1/2, PD98059 and CGRP 8-37 were able to inhibit CGRP-induced ERK1/2 phosphorylation. These results suggest that CGRP regulates the expression of VEGF through the CGRP receptor and ERK1/2 MAPK signaling pathway in human HaCaT keratinocytes.

• Authors: Xiao-Jing Yu, Chun-Yang Li, Ke-Yu Wang, Hong-Yan Dai
• Journal: Regulatory peptides (Regul Pept) Vol. 137 Issue 3 Pg. 134-9 (Dec 10 2006) ISSN: 0167-0115 [Print] Netherlands
• PMID: 16904202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Flavonoids
• RNA, Messenger
• Receptors, Calcitonin Gene-Related Peptide
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Calcitonin Gene-Related Peptide
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Base Sequence
• Calcitonin Gene-Related Peptide (pharmacology)
• Cell Line
• DNA Primers (genetics)
• Flavonoids (pharmacology)
• Gene Expression (drug effects)
• Humans
• Keratinocytes (drug effects, metabolism)
• MAP Kinase Signaling System (drug effects)
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
• Phosphorylation
• RNA, Messenger (genetics, metabolism)
• Receptors, Calcitonin Gene-Related Peptide (metabolism)
• Vascular Endothelial Growth Factor A (biosynthesis, genetics)