Hair follicle stem cell differentiation is inhibited through cross‐talk between Wnt/β‐catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia

Leirós, Gustavo José; Attorresi, Alejandra; Balañá, María Eugenia

doi:10.1111/j.1365-2133.2012.10856.x

Cited by 114 publications

(110 citation statements)

References 36 publications

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“…Several studies have suggested a relationship between β -catenin signaling and alopecia. When androgen treated DPC in androgenic alopecia patients, β -catenin was significantly decreased in the cytoplasm, while GSK-3 β was increased [36, 37]. BIO (GSK-3 β inhibitor) enhances hair-inducing ability through stabilization of β -catenin and elevated the alkaline phosphatase and insulin-growth factor-1 gene expressions [38, 39].…”

Section: Discussionmentioning

confidence: 99%

The Hair Growth‐Promoting Effect of Rumex japonicus Houtt. Extract

Lee

Kim

Yang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Rumex japonicus Houtt. is traditionally used as a medicinal plant to treat patients suffering from skin disease in Korea. However, the beneficial effect of Rumex japonicus Houtt. on hair growth has not been thoroughly examined. Therefore, the present study aims to investigate the hair growth-promoting effect of Rumex japonicus (RJ) Houtt. root extract using human dermal papilla cells (DPCs), HaCaT cells, and C57BL/6 mice model. RJ induced antiapoptotic and proliferative effects on DPCs and HaCaT cells by increasing Bcl-2/Bax ratio and activating cellular proliferation-related proteins, ERK and Akt. RJ also increased β-catenin via the inhibition of GSK-3β. In C57BL/6 mice model, RJ promoted the anagen induction and maintained its period. Immunohistochemistry analysis demonstrated that RJ upregulated Ki-67 and β-catenin expressions, suggesting that the hair growth effect of RJ may be mediated through the reinforcement of hair cell proliferation. These results provided important insights for the possible mechanism of action of RJ and its potential as therapeutic agent to promote hair growth.

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Section: Discussionmentioning

confidence: 99%

The Hair Growth‐Promoting Effect of Rumex japonicus Houtt. Extract

Lee

Kim

Yang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…The HF-enriched primary cultures (HFSCs) were obtained as previously described [34]. In brief, skin samples were incubated in 1 mg/ml collagenase/dispase (Sigma-Aldrich) overnight at 4°C, and telogen follicles were pulled out and incubated in 0.05% trypsin-0.23 mM EDTA (Gibco, Invitrogen, Life Technologies).…”

Section: Cell Culturesmentioning

confidence: 99%

“…The follicular dermal papilla cells can induce hair formation in rodents once they are located near the epithelium [31,32] or generate hair follicle neogenesis in vivo when combined with hair follicle stem cells [33]. The DPCs are also able to induce the differentiation of bulge stem cells into hair-lineage cell types in vitro [34,35].…”

Section: Introductionmentioning

confidence: 99%

Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

Leirós

Kusinsky

Drago³

et al. 2014

Stem Cells Translational Medicine

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Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and might contribute to the understanding of skin regeneration. The use of dermal papilla cells (DPCs) as a dermal component in a permanent composite skin with human hair follicle stem cells (HFSCs) was evaluated by studying the tissue-engineered skin architecture, stem cell persistence, hair regeneration, and graft-take in nude mice. A porcine acellular dermal matrix was seeded with HFSCs alone and with HFSCs plus human DPCs or dermal fibroblasts (DFs). In vitro, the presence of DPCs induced a more regular and multilayered stratified epidermis with more basal p63-positive cells and invaginations. The DPC-containing constructs more accurately mimicked the skin architecture by properly stratifying the differentiating HFSCs and developing a well-ordered epithelia that contributed to more closely recapitulate an artificial human skin. This acellular dermal matrix previously repopulated in vitro with HFSCs and DFs or DPCs as the dermal component was grafted in nude mice. The presence of DPCs in the composite substitute not only favored early neovascularization, good assimilation and remodeling after grafting but also contributed to the neovascular network maturation, which might reduce the inflammation process, resulting in a better healing process, with less scarring and wound contraction. Interestingly, only DPC-containing constructs showed embryonic hair bud-like structures with cells of human origin, presence of precursor epithelial cells, and expression of a hair differentiation marker. Although preliminary, these findings have demonstrated the importance of the presence of DPCs for proper skin repair.

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“…Therefore, the hairs regrow after the chemotherapy treatment is finished. In contrast, androgens inhibit Wnt signaling [48], which is required for the ability of the DP to induce hair cycling and regeneration [49]. This mechanism implies that targeting androgens as a therapy for AGA gives only a transient effect, while CIA can completely recover and hair growth becomes normal again.…”

Section: Androgenic Alopeciamentioning

confidence: 99%

Drug discovery for alopecia: gone today, hair tomorrow

Santos

Avci

Hamblin

2015

Expert Opinion on Drug Discovery

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Introduction Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. Areas covered In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8+NK group 2D-positive (NKG2D+) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. Expert opinion The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play.

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Hair follicle stem cell differentiation is inhibited through cross‐talk between Wnt/β‐catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia

Abstract: These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.

Cited by 114 publications

References 36 publications

The Hair Growth‐Promoting Effect of Rumex japonicus Houtt. Extract

The Hair Growth‐Promoting Effect of Rumex japonicus Houtt. Extract

Dermal Papilla Cells Improve the Wound Healing Process and Generate Hair Bud-Like Structures in Grafted Skin Substitutes Using Hair Follicle Stem Cells

Drug discovery for alopecia: gone today, hair tomorrow

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