Research Papers:

Neurokinin-1 receptor is a novel positive regulator of Wnt/β-catenin signaling in melanogenesis

Jia Zhou, Jingjing Ling, Huizhu Song, Bei Lv, Lei Wang, Jing Shang, Yong Wang, Chunyan Chang, Fengfeng Ping and Jun Qian _

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Oncotarget. 2016; 7:81268-81280. https://doi.org/10.18632/oncotarget.13222

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Jia Zhou1,*, Jingjing Ling2,*, Huizhu Song2, Bei Lv2, Lei Wang2, Jing Shang1, Yong Wang2, Chunyan Chang2, Fengfeng Ping2, Jun Qian2

1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China

2Wuxi People’s Hospital affiliated to Nanjing Medical University, Wuxi 214023, P.R. China

*These authors contributed equally to this work

Correspondence to:

Fengfeng Ping, email: [email protected]

Jun Qian, email: [email protected]

Keywords: neurokinin-1 receptor, Wnt/β-catenin, [Sar9, Met(O2)11] substance P, L-733060

Received: May 23, 2016     Accepted: November 02, 2016     Published: November 08, 2016


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.

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