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乳铁蛋白通过 Erk/Akt 和 Wnt 信号通路促进小鼠毛发生长,并增加真皮乳头细胞增殖。

Lactoferrin promotes hair growth in mice and increases dermal papilla cell proliferation through Erk/Akt and Wnt signaling pathways.

机构信息

Renorigin Innovation Institute Co. Ltd., Taipei, Taiwan.

Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Ren'ai Road, Taipei, 100, Taiwan.

出版信息

Arch Dermatol Res. 2019 Jul;311(5):411-420. doi: 10.1007/s00403-019-01920-1. Epub 2019 Apr 20.

Abstract

Hair loss affects men and women of all ages. Dermal papilla (DP) plays a crucial role in regulating the growth and cycling of hair follicles. Lactoferrin (LF) exhibits a wide range of biological functions, including antimicrobial activity and growth regulation. However, its effect on DP and its role in hair growth remain unknown. In this study, we found that bovine LF (bLF) promoted the proliferation of DP cells and enhanced the phosphorylation of Erk and Akt. The bLF-mediated proliferation was significantly blocked by the Erk phosphorylation inhibitor PD98059 or the Akt phosphorylation inhibitor LY294002. Moreover, biotin-labeled bLF could bind to DP cells, and the binding was independent of lipoprotein receptor-related protein 1, a known LF receptor. Importantly, bLF stimulated hair growth in both young and aged mice. Moreover, we also found that bLF significantly induced the expression of Wnt signaling-related proteins, including Wnt3a, Wnt7a, Lef1, and β-catenin. The bLF-mediated DP cell proliferation could be significantly reversed by the Wnt pathway inhibitor XAV939. Our findings suggest that bLF promotes hair growth in mice and stimulates proliferation of DP cells through Erk/Akt and Wnt signaling pathways. This study highlights a great potential of the use of bLF in developing drugs to treat hair loss.

摘要

脱发影响各个年龄段的男性和女性。真皮乳头(DP)在调节毛囊的生长和循环中起着至关重要的作用。乳铁蛋白(LF)表现出广泛的生物学功能,包括抗菌活性和生长调节。然而,它对 DP 的影响及其在毛发生长中的作用尚不清楚。在这项研究中,我们发现牛乳铁蛋白(bLF)促进 DP 细胞的增殖,并增强 Erk 和 Akt 的磷酸化。Erk 磷酸化抑制剂 PD98059 或 Akt 磷酸化抑制剂 LY294002 显著阻断了 bLF 介导的增殖。此外,生物素标记的 bLF 可以与 DP 细胞结合,这种结合不依赖于已知的 LF 受体脂蛋白受体相关蛋白 1。重要的是,bLF 刺激年轻和老年小鼠的毛发生长。此外,我们还发现 bLF 显著诱导 Wnt 信号相关蛋白的表达,包括 Wnt3a、Wnt7a、Lef1 和β-连环蛋白。Wnt 通路抑制剂 XAV939 可显著逆转 bLF 介导的 DP 细胞增殖。我们的研究结果表明,bLF 通过 Erk/Akt 和 Wnt 信号通路促进小鼠毛发生长,并刺激 DP 细胞增殖。这项研究强调了使用 bLF 开发治疗脱发药物的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aa4/6546667/008bd2df4d80/403_2019_1920_Fig1_HTML.jpg

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