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

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.

SUBMITTER: Sha K

PROVIDER: S-EPMC7476492 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Sha Ke K Chen Mengting M Liu Fangfen F Xu San S Wang Ben B Peng Qinqin Q Zhang Yiya Y Xie Hongfu H Li Ji J Deng Zhili Z

PeerJ 20200904

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 r ...[more]

PMID: 32953277

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Project description:BackgroundHair loss is a prevalent medical problem in both men and women. Maintaining the potential hair inductivity of dermal papilla cells (DPCs) during cell culture is the main factor in hair follicle morphogenesis and regeneration. The present study was conducted to compare the effects of different concentrations of human hair outer root sheath cell (HHORSC) and platelet lysis (PL) exosomes to maintain hair inductivity of the human dermal papilla cells (hDPCs).MethodsIn this study, hDPCs and HHORSCs were isolated from healthy hair samples. Specific markers of hDPCs (versican, α-SMA) and HHORSCs (K15) were evaluated using flow cytometric and immunocytochemical techniques. The exosomes were isolated from HHORSCs and PL with ultracentrifugation technique. Western blot was used to detect specific markers of HHORSCs and PL exosomes. Particle size and distribution of the exosomes were analyzed by NanoSight dynamic light NanoSight Dynamic Light Scattering. Different methods such as proliferation test (MTS assay), migration test (Transwell assay) were used to evaluate the effects of different concentrations of exosomes (2,550,100 µg/ml) derived from HHORSC and PL on hDPCs. Expression of specific genes in the hair follicle inductivity, including ALP, versican and α-SMA were also evaluated using real time-PCR.ResultsThe flow cytometry of the specific cytoplasmic markers of the hDPCs and HHORSCs showed expression of versican (77%), α-SMA (55.2%) and K15 (73.2%). The result of particle size and distribution of the exosomes were analyzed by NanoSight dynamic light NanoSight Dynamic Light Scattering, which revealed the majority of HHORSC and PL exosomes were 30-150 nm. For 100 µg/ml of HHORSC exosomes, the expressions of ALP, versican and α-SMA proteins respectively increased by a factor of 2.1, 1.7and 1.3 compared to those in the control group.ConclusionIn summary, we applied HHORSC exosomes as a new method to support hair inductivity of dermal papilla cells and improve the outcome for the treatment of hair loss.

Project description:Hair follicle regeneration is dependent on reciprocal signaling between epithelial cells and underlying mesenchymal cells within the dermal papilla. Hair follicle dermal stem cells reside within the hair follicle mesenchyme, self-renew in vivo, and function to repopulate the dermal papilla and regenerate the connective tissue sheath with each hair cycle. The identity and temporal pattern of signals that regulate hair follicle dermal stem cell function are not known. Here, we show that platelet-derived growth factor signaling is crucial for hair follicle dermal stem cell function and platelet-derived growth factor deficiency results in a progressive depletion of the hair follicle dermal stem cell pool and their progeny. Using αSMACreERT2:RosaYFP:Pdgfrαflox mice, we ablated Pdgfrα specifically within the adult hair follicle dermal stem cell lineage. This led to significant loss of hair follicle dermal stem cell progeny in connective tissue sheath and dermal papilla of individual follicles, and a progressive reduction in total number of anagen hair follicles containing YFP+ve cells. As well, over successive hair cycles, fewer hair follicle dermal stem cells were retained within each telogen hair follicle suggesting an impact on hair follicle dermal stem cell self-renewal. To further assess this, we grew prospectively isolated hair follicle dermal stem cells (Sox2GFP+ve αSMAdsRed+ve) in the presence or absence of platelet-derived growth factor ligands. Platelet-derived growth factor-BB enhanced proliferation, increased the frequency of Sox2+ve hair follicle dermal stem cell progeny and improved inductive capacity of hair follicle dermal stem cells in an ex vivo hair follicle formation assay. Similar effects on proliferation were observed in adult human SKPs. Our findings impart novel insights into the signals that comprise the adult hair follicle dermal stem cell niche and suggest that platelet-derived growth factor signaling promotes self renewal, is essential to maintain the hair follicle dermal stem cell pool and ultimately their regenerative capacity within the hair follicle.

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

Publications

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

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