Corticotropin-releasing hormone attenuates vascular endothelial growth factor release from human HaCaT keratinocytes.
OBJECTIVE
Corticotropin-releasing hormone (CRH) is a central component of the local hypothalamic-pituitary-adrenal (HPA) axis, which has a functional equivalent in the skin. To determine whether CRH and its receptor, CRH-R1, modulate the expression of vascular endothelial growth factor (VEGF), which is overexpressed in psoriatic epidermis and plays a causal role in the pathogenesis of psoriasis, we investigated the effect of CRH on the expression of VEGF in a human keratinocyte cell line (HaCaT) and whether this effect is via the mitogen-activated protein kinase (MAPK) signal transduction pathways.


METHODS
Real-time RT-PCR, ELISA assay and western blot were used in the present study to investigate the expression of VEGF in CRH-treated HaCaT cells.


RESULTS
The mRNA and protein levels of VEGF in CRH-treated HaCaT cells were significantly attenuated. However, this downregulation was abrogated by pretreatment with antalarmin, SB203580 and SP600125; pretreatment with PD98059 did not attenuate the effects of CRH on the expression of VEGF. In addition, CRH treatment induced rapid phosphorylation of p38 MAPK and JNK1/2, and antalarmin, SB203580 and SP600125 inhibited CRH-induced phosphorylation of p38 MAPK and JNK1/2.


CONCLUSIONS
CRH might downregulate the expression of VEGF through the CRH-R1 and MAPK (p38 MAPK and JNK1/2) signaling pathways in human HaCaT cells.
Zhou
Chun-Lei
CL
Department of Dermatology, Qilu Hospital, Shandong University, Jinan 250012, PR China.
Yu
Xiao-Jing
XJ
Chen
La-Mei
LM
Jiang
Hong
H
Li
Chun-Yang
CY
D015153:Blotting, Western; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D003346:Corticotropin-Releasing Hormone; D020929:Mitogen-Activated Protein Kinase Kinases