DKK3调控羊驼黑色素细胞中黑色素生成

DKK3 Regulates Melanogenesis in Melanocytes of Alpaca

Dickkopf-3(DKK3),Wnt/β-catenin信号通路中一个重要的抑制因子,可能参与调控黑色素生成过程。本文研究了DKK3在羊驼黑色素细胞中黑色素生成的作用。在羊驼黑色素细胞中,过表达DKK3显著下调Wnt1,Lef1,Myc和黑色素生成相关基因MITF及其下游基因TYR,TYRP1和TYRP2的表达,在mRNA和蛋白质水平均明显下降(P<0.05);总黑素,褐黑素和真黑素的含量分别下降80.30%、72.17%和64.60%(P<0.05)。相反,在羊驼黑色素细胞中转染siRNA-DKK3,一种小干扰RNA,可以显著上调Wnt1,Lef1,Myc和黑色素生成相关基因MITF及其下游基因TYR,TYRP1和TYRP2在mRNA和蛋白质水平的表达(P<0.05);总黑素、褐黑素和真黑素的含量分别增加1.65倍、1.25倍和1.21倍(P<0.05)。这些结果表明,DKK3可以通过Wnt/β-catenin信号通路介导MITF下调羊驼黑色素细胞中黑色素的生成。

Dickkopf-3(DKK3),as a critical inhibitor of the Wnt/β-catenin signaling pathway,may be involved in melanogenesis.In the current study,we investigated the effects of DKK3 on melanogenesis in melanocytes of alpaca.Overexpression of DKK3 in alpaca melanocytes,the expression of Wnt1,Lef1,Myc and the major target genes termed microphthalmia-associated transcription factor(MITF)and its downstream genes,including tyrosinase(TYR),tyrosinase-related protein 1(TYRP1)and tyrosinaserelated protein 2(TYRP2)were significantly decreased at both mRNA and protein levels(P<0.05);total alkali melanin,pheomelanin and eumelanin were decreased by 80.30%,72.17%and 64.60%(P<0.05),respectively.In contrast,in the melanocytes transfected with siRNA-DKK3(a small interference RNA targeting DKK3),the expression of Wnt1,Lef1,Myc,MITF,TYR,TYRP1 and TYRP2 were significantly increased at both mRNA and protein levels(P<0.05);total alkali melanin,pheomelanin and eumelanin were significantly increased by 1.65 folds,1.25 folds and 1.21 folds(P<0.05),respectively.These results indicate that DKK3 regulates melanogenesis in alpaca melanocytes via the Wnt/β-catenin signaling pathway and down-regulates MITF.