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

// Jia Zhou 1, * , Jingjing Ling 2, * , Huizhu Song 2 , Bei Lv 2 , Lei Wang 2 , Jing Shang 1 , Yong Wang 2 , Chunyan Chang 2 , Fengfeng Ping 2 , Jun Qian 2 1 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P.R. China 2 Wuxi 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: pfftile@163.com Jun Qian, email: Qianjun111@163.com 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 ABSTRACT 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, [Sar 9 , Met(O 2 ) 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.