Zhang Zhihui, Lei Mingxing, Xin Haoran, Hu Chunyan, Yang Tian, Xing Yizhan, Li Yuhong, Guo Haiying, Lian Xiaohua, Deng Fang
Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Department of Cell Biology, Third Military Medical University, Chongqing, China.
Oncotarget. 2017 Sep 1;8(41):69316-69327. doi: 10.18632/oncotarget.20613. eCollection 2017 Sep 19.
Canities is an obvious sign of aging in mouse and human, shown as hair graying. Melanocytes in the hair follicle show cyclic activity with hair cycling, which transitions from anagen, catagen to telogen. How the hairs turn gray during aging is not completely uncovered. Here, by using immunostaining and LacZ staining in Dct-LacZ mice, we show that β-catenin is expressed in melanocytes during hair cycling. RT-PCR, western blot and immunostaining show that β-catenin expression is significantly increased in both anagen and telogen skin of aged mice, when compared to the anagen and telogen skin of young mice, respectively. Overexpression of Wnt10b not only accelerates hair follicle to enter anagen phase, but also promotes melanocytes differentiation in young adult mice (2-month old), with increased β-catenin expression in melanocytes at the secondary hair germ and matrix region of regenerated hair follicles. Overexpression of Wnt10b also promotes melanocyte progenitor cells differentiation . Our data suggest that increased Wnt signaling promotes excessive differentiation of melanocytes, leading to exhaustion of melanocyte stem cells and eventually canities in aged mice.
白发是小鼠和人类衰老的一个明显标志，表现为毛发变白。毛囊中的黑素细胞随着毛发周期呈现周期性活动，毛发周期从生长期、退行期过渡到休止期。衰老过程中毛发如何变白尚未完全明确。在此，通过对Dct-LacZ小鼠进行免疫染色和LacZ染色，我们发现β-连环蛋白在毛发周期中表达于黑素细胞。逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法和免疫染色显示，与年轻小鼠的生长期和休止期皮肤相比，老年小鼠生长期和休止期皮肤中β-连环蛋白的表达均显著增加。在年轻成年小鼠（2月龄）中，Wnt10b的过表达不仅加速毛囊进入生长期，还促进黑素细胞分化，在再生毛囊的次级毛芽和基质区域的黑素细胞中β-连环蛋白表达增加。Wnt10b的过表达还促进黑素细胞祖细胞分化。我们的数据表明，Wnt信号增加促进黑素细胞过度分化，导致黑素干细胞耗竭，最终致使老年小鼠出现白发。
