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      Platelet factor 4 inhibits human hair follicle growth and promotes androgen receptor expression in human dermal papilla cells

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          Abstract

          Platelet-rich plasma (PRP) has been reported recently as a potential therapeutic approach for alopecia, such as androgenetic alopecia, but the exact mechanisms and effects of specific components of this recipe remain largely unknown. In this study, we identified that platelet factor 4 (PF4), a component of PRP, significantly suppressed human hair follicle growth and restrained the proliferation of human dermal papilla cells (hDPCs). Furthermore, our results showed that PF4 upregulated androgen receptor (AR) in human dermal papilla cells in vitro and via hair follicle organ culture. Among the hair growth-promoting and DP-signature genes investigated, PF4 decreased the expression of Wnt5a, Wnt10b, LEF1, HEY1 and IGF-1, and increased DKK1 expression , but did not affect BMP2 and BMP4 expression. Collectively, Our data demonstrate that PF4 suppresses human hair follicle growth possibly via upregulating androgen receptor signaling and modulating hair growth-associated genes, which provides thought-provoking insights into the application and optimization of PRP in treating hair loss.

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          The hair follicle as a dynamic miniorgan.

          Marlon R. Schneider, Ruth Schmidt-Ullrich, Ralf Paus (2009)
          Hair is a primary characteristic of mammals, and exerts a wide range of functions including thermoregulation, physical protection, sensory activity, and social interactions. The hair shaft consists of terminally differentiated keratinocytes that are produced by the hair follicle. Hair follicle development takes place during fetal skin development and relies on tightly regulated ectodermal-mesodermal interactions. After birth, mature and actively growing hair follicles eventually become anchored in the subcutis, and periodically regenerate by spontaneously undergoing repetitive cycles of growth (anagen), apoptosis-driven regression (catagen), and relative quiescence (telogen). Our molecular understanding of hair follicle biology relies heavily on mouse mutants with abnormalities in hair structure, growth, and/or pigmentation. These mice have allowed novel insights into important general molecular and cellular processes beyond skin and hair biology, ranging from organ induction, morphogenesis and regeneration, to pigment and stem cell biology, cell proliferation, migration and apoptosis. In this review, we present basic concepts of hair follicle biology and summarize important recent advances in the field.
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            Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt Pathway, Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development

            Pietro Gentile, Simone Garcovich (2019)
            The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (β-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).
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              Platelet chemokines in vascular disease.

              Christian Gleissner, Philipp von Hundelshausen, Klaus Ley (2008)
              Platelets are a rich source of different chemokines and express chemokine receptors. CXCL4 is highly abundant in platelets and involved in promoting monocyte arrest from rolling and monocyte differentiation to macrophages. CXCL4 can also associate with CCL5 and amplify its effect on monocytes. The megakaryocyte CXCL7 gene product is proteolytically cleaved into the strong neutrophil chemoattractant, NAP-2, which has also been implicated in repair cell homing to vascular lesions. Platelet adhesion can induce release of CCL2 and CXCL8 from endothelial cells. Conversely, the chemokines CCL17, CCL22, and CXCL12 made by other cells amplify platelet activation. Platelet chemokines enhance recruitment of various hematopoietic cells to the vascular wall, fostering processes such as neointima formation, atherosclerosis, and thrombosis, but also vessel repair and regeneration after vascular injury.
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                Author and article information

                Contributors
                Zhili Deng
                Journal
                Journal ID (nlm-ta): PeerJ
                Journal ID (iso-abbrev): PeerJ
                Journal ID (publisher-id): peerj
                Journal ID (pmc): peerj
                Title: PeerJ
                Publisher: PeerJ Inc. (San Diego, USA )
                ISSN (Electronic): 2167-8359
                Publication date (Electronic): 4 September 2020
                Publication date Collection: 2020
                Volume: 8
                Electronic Location Identifier: e9867
                Affiliations
                [1 ]Department of Dermatology, Xiangya Hospital, Central South University , Changsha, China
                [2 ]National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University , Changsha, China
                [3 ]Key Laboratory of Molecular Radiation Oncology Hunan Province, Central South University , Changsha, China
                [4 ]Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Central South University , Changsha, China
                [5 ]Xiangya International Academy of Translational Medicine, Central South University , Changsha, China
                Article
                Publisher ID: 9867
                DOI: 10.7717/peerj.9867
                PMC ID: 7476492
                PubMed ID: 32953277
                SO-VID: c5f7db26-4ac6-46f3-a8f2-4f32872710e9
                Copyright © ©2020 Sha et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                Date received : 12 February 2020
                Date accepted : 13 August 2020
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81773351
                Award ID: 91749114
                Award ID: 81874251
                Award ID: 81703149
                Award ID: 81602789
                This work was supported by the National Natural Science Foundation of China (No. 81773351, No. 91749114, No. 81874251, No. 81703149, No. 81602789). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Cell Biology
                Subject: Molecular Biology
                Subject: Andrology
                Subject: Dermatology
                Subject: Translational Medicine

                Keywords: hair loss,hair follicle,platelet-rich plasma,platelet factor 4,androgen receptor,dermal papilla cells
                Data availability:
                Keywords: hair loss, hair follicle, platelet-rich plasma, platelet factor 4, androgen receptor, dermal papilla cells

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