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

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          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.

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          Most cited references31

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          Cellular survival: a play in three Akts.

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            The secret life of the hair follicle.

            M. Hardy (1992)
            The mammalian hair follicle is a treasure waiting to be discovered by more molecular geneticists. How can a tiny cluster of apparently uniform epithelial cells, adjacent to a tiny cluster of uniform mesenchymal cells, give rise to five or six concentric cylinders, each of which is composed of cells of a distinctive type that synthesize their own distinctive set of proteins? There is now evidence that several growth factors, cell adhesion molecules and other molecules play important roles in the regulation of this minute organ.
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              Mammalian lactoferrin receptors: structure and function.

              Mammalian lactoferrin (Lf) receptors are suggested to have pivotal roles for mediating multiple functions of Lf. In this review, we focus on current knowledge of the structure and function of mammalian Lf receptors, mainly the first cloned Lf receptor that has been shown to be expressed in the infant small intestine at high levels but also in virtually all other tissues. The small intestinal Lf receptor takes up iron from Lf into cells and presumably exerts other physiological functions. Other Lf receptors in various tissues have also been reported to mediate some functions of Lf, such as modulating immune function, inhibiting platelet aggregation and enhancing collagen gel contractile strength. The detailed mechanisms behind the receptor-Lf interactions still need to be elucidated.
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                Author and article information

                Contributors
                886-2-23123456 , mchuang@ntu.edu.tw
                Journal
                Arch Dermatol Res
                Arch. Dermatol. Res
                Archives of Dermatological Research
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-3696
                1432-069X
                20 April 2019
                20 April 2019
                2019
                : 311
                : 5
                : 411-420
                Affiliations
                [1 ]Renorigin Innovation Institute Co. Ltd., Taipei, Taiwan
                [2 ]ISNI 0000 0004 0546 0241, GRID grid.19188.39, Graduate Institute of Anatomy and Cell Biology, College of Medicine, , National Taiwan University, ; No. 1, Sec. 1, Ren’ai Road, Taipei, 100 Taiwan
                Article
                1920
                10.1007/s00403-019-01920-1
                6546667
                31006055
                3e368325-70cd-42b8-976f-abf878c8623d
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 5 October 2018
                : 4 March 2019
                : 13 April 2019
                Categories
                Original Paper
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Dermatology
                lactoferrin,alopecia,hair,dermal papilla
                Dermatology
                lactoferrin, alopecia, hair, dermal papilla

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