Neurokinin-1 receptor is a novel positive regulator of Wnt/ β-catenin signaling in melanogenesis.
Wnt/β-catenin signaling is essential for melanogenesis in melanocytes. Neurokinin-1 receptor (NK-1R) has recently been demonstrated to be involved in melanin production. However, the cross talk between NK-1R and Wnt/β-catenin is poorly understood. Here, [Sar9, Met(O2)11] substance P (SMSP) was used to activate NK-1R, while L-733060 was used to inhibit it. The effects of NK-1R activation and inhibition on Wnt and its inhibitors were analyzed using western blot and real-time quantitative PCR. The results showed that SMSP positively regulated Wnt/β-catenin signaling by increasing the expression of β-catenin and p-GSK3β protein, which resulted from the weakened expression of the Wnt inhibitor Dickkopf-1 (DKK1). On the contrary, L-733060 lowered the expression of β-catenin and p-GSK3β protein through the up-regulation of DKK1 expression. Furthermore, in L-733060-treated mice, it was found that the pigmentation level as well as the melanogenic proteins and β-catenin protein expression were down-regulated, while the expression of DKK1 was up-regulated. These results showed the interaction between NK-1R and Wnt in human melanocytes in vitro and C57BL/6J mice in vivo, indicating that NK-1R may positively regulate melanogenesis through Wnt/β-catenin signaling pathway.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
Jia
J
Zhou
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China.
Jingjing
J
Ling
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China.
Huizhu
H
Song
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China.
Bei
B
Lv
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China.
Lei
L
Wang
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China.
Jing
J
Shang
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China.
Yong
Y
Wang
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China.
Chunyan
C
Chang
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China.
Fengfeng
F
Ping
Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China.
Jun
J
Qian
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D010766:Phosphorylation; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012880:Skin Pigmentation / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C501126:DKK1 protein, human; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D051176:beta Catenin; C062618:substance P, Sar(9)-Met(O2)(11)-; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D013373:Substance P; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse
L-733060; Met(O2)11] substance P; Wnt/β-catenin; [Sar9; neurokinin-1 receptor