Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia

Leirós, Gustavo José; Ceruti, Julieta María; Castellanos, María Lía; Kusinsky, Ana Gabriela; Balañá, María Eugenia

doi:10.1016/j.mce.2016.10.018

Cited by 59 publications

(59 citation statements)

References 36 publications

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“…The Wnt/β-catenin pathway is crucial for the proliferation of dermal papilla cells and hair growth [28]. Therefore, we addressed whether U. peterseniana extract could activate the Wnt/β-catenin pathway.…”

Section: Resultsmentioning

confidence: 99%

“…The Wnt/β-catenin pathway is one of the master regulator of cell growth in several cell types, including hair follicle SC and pancreatic beta cells [28,38], and is inhibited by GSK-3β [39,40]. Previous findings suggested that the inactivation of GSK-3β by LiCl, an inhibitor of GSK-3β, led to a decrease in the ubiquitination of β-catenin, which resulted in the phosphorylation and translocation of β-catenin into the nucleus [40].…”

Section: Discussionmentioning

confidence: 99%

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Undariopsis peterseniana Promotes Hair Growth by the Activation of Wnt/β-Catenin and ERK Pathways

et al. 2017

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In this study, we investigated the effect and mechanism of Undariopsis peterseniana, an edible brown alga, on hair growth. The treatment of vibrissa follicles with U. peterseniana extract ex vivo for 21 days significantly increased the hair-fiber lengths. The U. peterseniana extract also significantly accelerated anagen initiation in vivo. Moreover, we found that U. peterseniana extract was able to open the KATP channel, which may contribute to increased hair growth. The U. peterseniana extract decreased 5α-reductase activity and markedly increased the proliferation of dermal papilla cells, a central regulator of the hair cycle. The U. peterseniana extract increased the levels of cell cycle proteins, such as Cyclin D1, phospho(ser780)-pRB, Cyclin E, phospho-CDK2, and CDK2. The U. peterseniana extract also increased the phosphorylation of ERK and the levels of Wnt/β-catenin signaling proteins such as glycogen synthase kinase-3β (GSK-3β) and β-catenin. These results suggested that the U. peterseniana extract had the potential to influence hair growth by dermal papilla cells proliferation through the activation of the Wnt/β-catenin and ERK pathways. We isolated a principal of the U. peterseniana extract, which was subsequently identified as apo-9′-fucoxanthinone, a trichogenic compound. The results suggested that U. peterseniana extract may have a pivotal role in the treatment of alopecia.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Undariopsis peterseniana Promotes Hair Growth by the Activation of Wnt/β-Catenin and ERK Pathways

et al. 2017

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“…Previous studies have found that androgen has different effects on hair follicles in different regions, and appropriate concentrations of androgens can promote hair growth, while excessive concentrations of androgens can inhibit hair growth (Itami and Inui, 2005). Dermal papilla cells (DPC) can induce hair follicle stem cells (HFSC) to differentiate into hair follicles, while DHT inhibits HFSC differentiation by interfering with Wnt pathway in a coculture model with human DPC and HFSC (Leirós et al, 2012;Leirós et al, 2017). Of course, these studies have given us a much clearer understanding of the growth of hair follicles, but we also have found that these studies have not been fully verified from the organ level.…”

Section: Discussionmentioning

confidence: 99%

Dihydrotestosterone Regulates Hair Growth Through the Wnt/β-Catenin Pathway in C57BL/6 Mice and In Vitro Organ Culture

Chen

Liu

et al. 2020

Front. Pharmacol.

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Dihydrotestosterone (DHT) is the most potent androgen that regulates hair cycling. Hair cycling involves cross-talk between the androgen and Wnt/b-catenin pathways. However, how DHT regulates hair follicle (HF) growth through the Wnt/b-catenin pathway has not been well investigated. This study aimed to investigate the roles of DHT in hair growth in vivo and in vitro. Human scalp HFs were treated with different concentrations of DHT (10-5 , 10-6 , 10-7 , 10-8 , and 10-9 mol/L) for 10 days. The effects of DHT on hair shaft elongation, the proliferation of hair matrix cells, and the levels of b-catenin, GSK-3b, and phosphorylated GSK-3b (ser9) were evaluated in the cultured HFs. The effects of DHT were further investigated in C57BL/6 mice. Moreover, the growth of cultured human HFs was observed after interfering with the bcatenin pathway through inhibitors or activators in the presence or absence of DHT. We found that different concentrations of DHT had different effects on human HFs in vitro and C57BL/6 mice. At 10-6 mol/L, DHT inhibited HF growth and b-catenin/p-GSK-3b expression, whereas 10-7 mol/L DHT induced HF growth and b-catenin/p-GSK-3b expression. In addition, a bcatenin inhibitor (21H7) inhibited HF growth in vitro, while a b-catenin activator (IM12) promoted HF growth in vitro and antagonized the inhibition of HFs by high levels of DHT. These results suggest that DHT plays a pivotal role in region-specific hair growth, which may be related to the Wnt/b-catenin pathway.

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“…Testosterone and DHT exert their inhibitory effects on DPCs via multiple markers . A testosterone analogue Stanozolol (17 β ‐hydroxy‐17 α ‐methyl‐5 α ‐androst‐2‐eno[3,2c]pyrazol) and a synthetic androgen, methyltrienolone (R1881) exhibited inhibitory effects on DPCs .1 α ,25‐dihydroxyvitamin D3 (VD3) also demonstrated inhibition of DPCs activity .…”

Section: Hair Growth Inhibitory Effectmentioning

confidence: 99%

Review of Hair Follicle Dermal Papilla cells asin vitroscreening model for hair growth

Madaan

Verma

Singh

et al. 2018

Intern J of Cosmetic Sci

125

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Hair disorders such as hair loss (alopecia) and androgen dependent, excessive hair growth (hirsutism, hypertrichosis) may impact the social and psychological well-being of an individual. Recent advances in understanding the biology of hair have accelerated the research and development of novel therapeutic and cosmetic hair growth agents. Preclinical models aid in dermocosmetic efficacy testing and claim substantiation of hair growth modulators. The in vitro models to investigate hair growth utilize the hair follicle Dermal Papilla cells (DPCs), specialized mesenchymal cells located at the base of hair follicle that play essential roles in hair follicular morphogenesis and postnatal hair growth cycles. In this review, we have compiled and discussed the extensively reported literature citing DPCs as in vitro model to study hair growth promoting and inhibitory effects. A variety of agents such as herbal and natural extracts, growth factors and cytokines, platelet-rich plasma, placental extract, stem cells and conditioned medium, peptides, hormones, lipid-nanocarrier, light, electrical and electromagnetic field stimulation, androgens and their analogs, stress-serum and chemotherapeutic agents etc. have been examined for their hair growth modulating effects in DPCs. Effects on DPCs' activity were determined from untreated (basal) or stress induced levels. Cell proliferation, apoptosis and secretion of growth factors were included as primary end-point markers. Effects on a wide range of biomolecules and mechanistic pathways that play key role in the biology of hair growth were also investigated. This consolidated and comprehensive review summarizes the up-to-date information and understanding regarding DPCs based screening models for hair growth and may be helpful for researchers to select the appropriate assay system and biomarkers. This review highlights the pivotal role of DPCs in the forefront of hair research as screening platforms by providing insights into mechanistic action at cellular level, which may further direct the development of novel hair growth modulators.

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Androgens modify Wnt agonists/antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia

Cited by 59 publications

References 36 publications

Undariopsis peterseniana Promotes Hair Growth by the Activation of Wnt/β-Catenin and ERK Pathways

Undariopsis peterseniana Promotes Hair Growth by the Activation of Wnt/β-Catenin and ERK Pathways

Dihydrotestosterone Regulates Hair Growth Through the Wnt/β-Catenin Pathway in C57BL/6 Mice and In Vitro Organ Culture

Review of Hair Follicle Dermal Papilla cells asin vitroscreening model for hair growth

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