Calcitonin gene-related peptide regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes by activation of ERK1/2 MAPK.
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.
Yu
Xiao-Jing
XJ
Department of Dermatology, Qilu Hospital, University of Shandong, Jinan 250-012, China.
Li
Chun-Yang
CY
Wang
Ke-Yu
KY
Dai
Hong-Yan
HY
D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics*
D017931:DNA Primers; D005419:Flavonoids; D012333:RNA, Messenger; D018015:Receptors, Calcitonin Gene-Related Peptide; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015740:Calcitonin Gene-Related Peptide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one