期刊
REGULATORY PEPTIDES
卷 137, 期 3, 页码 134-139出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.regpep.2006.07.001
关键词
psoriasis; CGRP; VEGF; angiogenesis; ERK1/2
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 ERK 1/2, PD98059 and CGRP 8-37 were able to inhibit CGRP-induced ERK 1/2 phosphorylation. These results suggest that CGRP regulates the expression of VEGF through the CGRP receptor and ERK 1/2 MAPK signaling pathway in human HaCaT keratinocytes. (c) 2006 Elsevier B.V. All rights reserved.
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