Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.

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Morus alba Root Extract Induces the Anagen Phase in the Human Hair Follicle Dermal Papilla Cells

Pharmaceutics ◽

10.3390/pharmaceutics13081155 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1155

Author(s):

Jiyu Hyun ◽

Jisoo Im ◽

Sung-Won Kim ◽

Han Young Kim ◽

Inwoo Seo ◽

...

Keyword(s):

Hair Follicle ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Follicles ◽

Morus Alba ◽

Root Extract ◽

Dermal Papilla Cells ◽

Anagen Phase ◽

Factor Secretion ◽

Growth Factor Secretion

Restoring hair follicles by inducing the anagen phase is a promising approach to prevent hair loss. Hair follicle dermal papilla cells (HFDPCs) play a major role in hair growth via the telogen-to-anagen transition. The therapeutic effect of Morus alba activates β-catenin in HFDPCs, thereby inducing the anagen phase. The HFDPCs were treated with M. alba root extract (MARE) to promote hair growth. It contains chlorogenic acid and umbelliferone and is not cytotoxic to HFDPCs at a concentration of 20%. It was demonstrated that a small amount of MARE enhances growth factor secretion (related to the telogen-to-anagen transition). Activation of β-catenin was observed in MARE-treated HFDPCs, which is crucial for inducing the anagen phase. The effect of conditioned medium derived from MARE-treated HFDPCs on keratinocytes and endothelial cells was also investigated. The findings of this study demonstrate the potency of MARE in eliciting the telogen-to-anagen transition.

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The induction of hair follicle formation in the adult hooded rat by vibrissa dermal papillae

Development ◽

10.1242/dev.23.1.219 ◽

1970 ◽

Vol 23 (1) ◽

pp. 219-236

Author(s):

R. F. Oliver

Keyword(s):

Hair Follicle ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Shaft ◽

Hair Follicles ◽

Hair Cycle ◽

Hair Bulb ◽

Essential Component ◽

Dermal Papillae

Hair follicles are essentially composed of two tissues. The inner epidermal component, which gives rise to, among other products, the keratinized hair shaft, is confluent with the surface epidermis and is ensheathed by the dermal component which is confluent with the pars papillaris of the dermis. A specialization of the dermal component is the dermal papilla which, in follicles producing hair, is enclosed by the epidermal matrix of the hair bulb and is connected to the dermal sheath by the papilla stalk. Many authorities have considered that the dermal papilla is an essential component of the hair follicle (reviews: Cohen, 1965; Oliver, 1969). It has been suggested that the dermal papilla may be involved in both the induction of follicle lengthening and hair growth during the proanagen phase (Chase, 1965) of the hair cycle, a concept now justified by direct experimentation in the vibrissa follicle at least (Oliver, 1967b), and perhaps also in determining the nature of the hair produced by a follicle.

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Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth

International Journal of Molecular Sciences ◽

10.3390/ijms21165672 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5672

Author(s):

Kyung-Eun Ku ◽

Nahyun Choi ◽

Jong-Hyuk Sung

Keyword(s):

Hair Growth ◽

Expression Patterns ◽

Dermal Papilla ◽

Hair Follicles ◽

Hair Cycle ◽

Outer Root Sheath ◽

Dermal Papilla Cells ◽

Root Sheath ◽

Culture Models

Rab27a/b are known to play an important role in the transport of melanosomes, with their knockout causing silvery gray hair. However, the relationship between Rab27a/b and hair growth is not well known. To evaluate the role of Rab27a/b in hair cycle, we investigated the expression of Rab27a/b during hair cycling and human outer root sheath (hORS) cells. The expression of Rab27a in ORS cells was mainly detected at the anagen, whereas expression of Rab27b in ORS, and epidermal cells was strongly expressed at the telogen. Additionally, Rab27a/b were expressed in the Golgi of hORS cells. To evaluate the role of Rab27a/b in hair growth, telogen-to-anagen transition animal and vibrissae hair follicles (HFs) organ culture models were assayed using Rab27a/b siRNAs. The knockdown of Rab27a or Rab27b suppressed or promoted hair growth, respectively. These results were also confirmed in human dermal papilla cells (hDPCs) and hORS cells, showing the opposite mitogenic effects. Moreover, Rab27b knockdown increased the expression levels of various growth factors in the hDPCs and hORS cells. Overall, the opposite temporal expression patterns during hair cycling and roles for hair growth of Rab27a/b suggested that Rab27a/b might regulate the hair cycle. Therefore, our study may provide a novel solution for the development of hair loss treatment by regulating Rab27a/b levels.

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Molecular Pathways Involved in Promoting Activity of Timosaponin BII on Hair Growth in C57BL/6 Mice

BioMed Research International ◽

10.1155/2020/9451596 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Lei Xiao ◽

Xia Zhang ◽

Zhiyi Chen ◽

Jianhua Li ◽

Bing Li ◽

...

Keyword(s):

Hair Follicle ◽

Hair Growth ◽

Immunohistochemical Analysis ◽

Hair Follicles ◽

Common Disease ◽

Male Mice ◽

High Concentration ◽

Anagen Phase ◽

Approved Drugs ◽

Anemarrhena Asphodeloides

Hair loss is a common disease in dermatology, while the approved drugs may have unpredictable side effects. In this study, the effect of timosaponin BII extracted from Anemarrhena asphodeloides on hair growth of C57BL/6 mice was investigated by measuring the hair follicle morphology, hair growth length and area in C57BL/6 male mice, and the immunohistochemical analysis of β-catenin, Wnt3a, and Wnt10b in the dorsal skins of mice after topical application with minoxidil and timosaponin BII for 15 days. The decrease in skin brightness, the increase in the regrowing area of hair and hair follicles numbers, and the improvement of hair follicle morphology in the group applied with 0.5% timosaponin BII indicated an induction of the anagen phase in telogenic mice skin, which were comparative to the 2% minoxidil treatment. The immunohistochemical analysis detected an increase in the expression of β-catenin and Wnt10b, supporting the theory of the activation of the β-catenin/Wnt pathway was one of the pathways that are related to anagen phase induction. Anemarrhena asphodeloides is a herb commonly used for metabolic disorders in China. The present study is the first to show that the timosaponin BII, which is present at a high concentration in A. asphodeloides, promotes hair growth in C57BL/6 male mice. The results indicate that timosaponin BII may be a potential promoting agent for hair growth.

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Plakoglobin Suppresses Epithelial Proliferation and Hair Growth in Vivo

The Journal of Cell Biology ◽

10.1083/jcb.149.2.503 ◽

2000 ◽

Vol 149 (2) ◽

pp. 503-520 ◽

Cited By ~ 80

Author(s):

Emmanuelle Charpentier ◽

Robert M. Lavker ◽

Elizabeth Acquista ◽

Pamela Cowin

Keyword(s):

Hair Growth ◽

Cultured Cells ◽

Hair Follicles ◽

Tumor Formation ◽

Hair Cycle ◽

Epithelial Proliferation ◽

Desmosomal Cadherins ◽

Hair Follicle Cycle

Plakoglobin regulates cell adhesion by providing a modulatable connection between both classical and desmosomal cadherins and their respective cytoskeletal linker proteins. Both plakoglobin and the related protein β-catenin are posttranscriptionally upregulated in response to Wnt-1 in cultured cells. Upregulation of β-catenin has been implicated in potentiating hyperproliferation and tumor formation. To investigate the role of plakoglobin in these functions we expressed a full-length (PG) and an NH2-terminally truncated form of plakoglobin (ΔN80PG) in mouse epidermis and hair follicles, tissues which undergo continuous and easily observed postnatal renewal and remodeling. Expression of these constructs results in stunted hair growth, a phenotype that has also been observed in transgenic mice expressing Wnt3 and Dvl2 (Millar et al. 1999). Hair follicles from PG and ΔN80PG mice show premature termination of the growth phase (anagen) of the hair cycle, an event that is regulated in part by FGF5 (Hebert et al. 1994). The proliferative rate of the epidermal cells was reduced and apoptotic changes, which are associated with entry into the regressive phase of the hair follicle cycle (catagen), occurred earlier than usual.

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HNG, A Humanin Analogue, Promotes Hair Growth by Inhibiting Anagen-to-Catagen Transition

International Journal of Molecular Sciences ◽

10.3390/ijms21124553 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4553

Author(s):

Sung Min Kim ◽

Jung-Il Kang ◽

Hoon-Seok Yoon ◽

Youn Kyung Choi ◽

Ji Soo Go ◽

...

Keyword(s):

Hair Follicle ◽

Hair Growth ◽

Cell Cycle Progression ◽

Dermal Papilla ◽

Follicle Cell ◽

Hair Shaft ◽

Promoting Effect ◽

Dermal Papilla Cells ◽

Anagen Phase

The hair follicle goes through repetitive cycles including anagen, catagen, and telogen. The interaction of dermal papilla cells (DPCs) and keratinocytes regulates the hair cycle and hair growth. Humanin was discovered in the surviving brain cells of patients with Alzheimer’s disease. HNG, a humanin analogue, activates cell growth, proliferation, and cell cycle progression, and it protects cells from apoptosis. This study was performed to investigate the promoting effect and action mechanisms of HNG on hair growth. HNG significantly increased DPC proliferation. HNG significantly increased hair shaft elongation in vibrissa hair follicle organ culture. In vivo experiment showed that HNG prolonged anagen duration and inhibited hair follicle cell apoptosis, indicating that HNG inhibited the transition from the anagen to catagen phase mice. Furthermore, HNG activated extracellular signal-regulated kinase (Erk)1/2, Akt, and signal transducer and activator of transcription (Stat3) within minutes and up-regulated vascular endothelial growth factor (VEGF) levels on DPCs. This means that HNG could induce the anagen phase longer by up-regulating VEGF, which is a Stat3 target gene and one of the anagen maintenance factors. HNG stimulated the anagen phase longer with VEGF up-regulation, and it prevented apoptosis by activating Erk1/2, Akt, and Stat3 signaling.

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What Can Complex Dietary Supplements Do for Hair Loss and How Can It Be Validly Measured—A Review

Applied Sciences ◽

10.3390/app10144996 ◽

2020 ◽

Vol 10 (14) ◽

pp. 4996

Author(s):

Nicole Braun ◽

Ulrike Heinrich

Keyword(s):

Hair Follicle ◽

Dietary Supplements ◽

Hair Loss ◽

Hair Growth ◽

Hair Cycle ◽

Active Growth ◽

Widespread Occurrence ◽

Non Invasive ◽

Anagen Phase

Hair plays a major role in perception within a society. It provides information about gender, age, health, and social status. It is therefore not surprising that those affected are exposed to great suffering due to the widespread occurrence of hair loss. As a result, the demand for new products to remedy this problem is not diminishing. Hair grows in cycles, and a hair follicle goes through several phases called the hair cycle. The active growth phase (anagen phase) lasts 2–6 years. In this state a hair follicle shows a growth of about 1 cm per month. In order to improve the existing hair status, hair should be kept in the active anagen phase as long as possible, or the transition to anagen should be stimulated. A number of reviews already describe the influence of individual active ingredients on hair growth. However, the following review describes existing studies of complex dietary supplements with their experimental weaknesses and strengths and their influence on hair loss. Also, for the determination of hair loss, it is important to use a valid method with high acceptance by the test persons. In this context, the TrichoScale® is a validated and non-invasive tool for quantifying hair loss/hair growth. Thus, it is an ideal measuring instrument to objectively quantify the effectiveness of a hair loss treatment.

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Expression of decorin throughout the murine hair follicle cycle: hair cycle dependence and anagen phase prolongation

Experimental Dermatology ◽

10.1111/exd.12441 ◽

2014 ◽

Vol 23 (7) ◽

pp. 486-491 ◽

Cited By ~ 12

Author(s):

Jing Jing ◽

Xian-jie Wu ◽

Yun-ling Li ◽

Sui-Qing Cai ◽

Min Zheng ◽

...

Keyword(s):

Hair Follicle ◽

Hair Cycle ◽

Anagen Phase ◽

Hair Follicle Cycle ◽

Cycle Dependence

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CD133-positive dermal papilla-derived Wnt ligands regulate postnatal hair growth

Biochemical Journal ◽

10.1042/bcj20160466 ◽

2016 ◽

Vol 473 (19) ◽

pp. 3291-3305 ◽

Cited By ~ 4

Author(s):

Linli Zhou ◽

Kun Yang ◽

April Carpenter ◽

Richard A. Lang ◽

Thomas Andl ◽

...

Keyword(s):

Hair Follicle ◽

Hair Growth ◽

Dermal Papilla ◽

Hair Shaft ◽

Hair Follicles ◽

Proliferation And Differentiation ◽

Wnt Ligands ◽

Epithelial Compartment ◽

Hair Follicle Growth

Active Wnt/β-catenin signaling in the dermal papilla (DP) is required for postnatal hair cycling. In addition, maintenance of the hair-inducing ability of DP cells in vitro requires external addition of Wnt molecules. However, whether DP cells are a critical source of Wnt ligands and induce both autocrine and paracrine signaling cascades to promote adult hair follicle growth and regeneration remains elusive. To address this question, we generated an animal model that allows inducible ablation of Wntless (Wls), a transmembrane Wnt exporter protein, in CD133-positive (CD133+) DP cells. CD133+ cells have been shown to be a specific subpopulation of cells in the DP, which possesses the hair-inducing capability. Here, we show that ablation of Wls expression in CD133+ DP cells results in a shortened period of postnatal hair growth. Mutant hair follicles were unable to enter full anagen (hair growth stage) and progressed toward a rapid regression. Notably, reduced size of the DP and decreased expression of anagen DP marker, versican, were observed in hair follicles when CD133+ DP cells lost Wls expression. Further analysis showed that Wls-deficient CD133+ DP cells led to reduced proliferation and differentiation in matrix keratinocytes and melanocytes that are needed for the generation of the hair follicle structure and a pigmented hair shaft. These findings clearly demonstrate that Wnt ligands produced by CD133+ DP cells play an important role in postnatal hair growth by maintaining the inductivity of DP cells and mediating the signaling cross-talk between the mesenchyme and the epithelial compartment.

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Single-cell sequencing reveals the intermediate cell state and function of dermal papilla cells in the hair follicle cycle of cashmere goats

10.21203/rs.3.rs-25379/v1 ◽

2020 ◽

Author(s):

Feng Yang ◽

Zhihong Liu ◽

Tianyu Che ◽

Juntao Guo ◽

Yuchun Xie ◽

...

Keyword(s):

Hair Follicle ◽

Progenitor Cells ◽

Dermal Papilla ◽

Hair Follicles ◽

Intermediate Cell ◽

Dermal Papilla Cells ◽

Cashmere Goats ◽

Hair Follicle Cycle ◽

Intermediate Cells ◽

And Function

Abstract Background: Human hair loss and regeneration has stimulated interest in the natural hair cycle worldwide; however, such research is difficult because the periodicity of human or mouse hair is not visually obvious. Dermal papilla cells (DP cells) play an important role in the development of hair follicles, but knowledge of the differentiation and mechanisms of DP stem cells during transition through the hair follicle cycle are still limited, although some studies have reported that DP cells may have an intermediate cell state during differentiation, the classification and function of specific cell states are not clear. Results: Here, we used cashmere goats, that have obvious periodicity of hair follicles, as model animals and, based on unbiased single cell RNA sequencing, we identified and isolated DP cell data. Pseudotime ordering analysis was used to successfully construct a DP cell lineage differentiation trajectory and revealed the sequential activation of key genes, signaling pathways, and functions involved in cell fate decisions. At the same time, we analyzed the mechanisms of different cell fates and revealed the function of four different intermediate cells: Intermediate cells 10 showed important functions in the growth of cashmere and maintenance of cashmere attachment to the skin; intermediate cells 1 revealed important functions in the process of apoptosis and cashmere shedding of secondary hair follicles; intermediate cells 0 initiated new follicular cycles and completed the migration of hair follicles and the occurrence of cashmere; and intermediate cells 15 are suggested to be DP progenitor cells. Conclusions: In development and apoptosis, inner bulge cells not only earlier than outer bulge cells, but occurred faster and was more thorough,this helps a deeper understanding of the role of bulge cells. Pseudogenes play another important role in function which promoted the competitive endogenous RNA (ceRNA) hybridization of pseudogenes.In different hair follicle cycles, DP cells will differentiate into different intermediate state cells and perform different functions, and the marker genes of the cells also changed. Intermediate cells 10 showed important functions in the growth of cashmere and maintenance of cashmere attachment to the skin; intermediate cells 1 revealed important functions in the process of apoptosis and cashmere shedding of secondary hair follicles; intermediate cells 0 initiated new follicular cycles and completed the migration of hair follicles and the occurrence of cashmere; and intermediate cells 15 are DP progenitor cells, this conclusion provides an unprecedented deeper understanding of the function of DP cells.

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