Hair Follicle Cycling Research Articles

DNA methylation and histone acetylation are involved in Wnt10b expression during the secondary hair follicle cycle in Angora rabbits.

Secondary hair follicles (SHFs) in the Angora rabbit exhibit classic cyclic hair development, but the multiple molecular signals involved in hair cycling are yet to be explored in detail. In the present study, we investigated the expression pattern, methylation and histone H3 acetylation status of Wnt10b, as a molecular signal participating in hair cycling, during the SHF cycle in the Angora rabbit. Expression of Wnt10b at the anagen phase was significantly higher than that at both the telogen and catagen phases, suggesting that Wnt10b might serve as a critical activator during cyclic transition of SHFs. Methylation frequency of the fifth CpG site (CpG5-175bp) in CpG islands at the anagen phase was lower than that at both the catagen and telogen phases. The methylation status of the CpG5 site was negatively correlated with Wnt10b expression. This indicated that the methylation of CpG5 might participate in Wnt10b transcriptional suppression in SHFs. Furthermore, histone H3 acetylation status in the regions-256~-11bp and 98~361bp were significantly lower at both the catagen and telogen phases than at the anagen phase. The histone H3 acetylation level was significantly positively correlated with Wnt10b expression. This confirmed that histone acetylation was likely involved in upregulating Wnt10b transcription in SHFs. Additionally, potential binding to the transcription factors ZF57 and HDBP was predicted within the CpG5 site. In conclusion, our findings reveal the epigenetic mechanism of Wnt10b transcription and provide a new insight into epigenetic regulation during the SHF cycle in the Angora rabbit.

Multiple potential roles of thymosin β4 in the growth and development of hair follicles.

The hair follicle (HF) is an important mini‐organ of the skin, composed of many types of cells. Dermal papilla cells are important signalling components that guide the proliferation, upward migration and differentiation of HF stem cell progenitor cells to form other types of HF cells. Thymosin β4 (Tβ4), a major actin‐sequestering protein, is involved in various cellular responses and has recently been shown to play key roles in HF growth and development. Endogenous Tβ4 can activate the mouse HF cycle transition and affect HF growth and development by promoting the migration and differentiation of HF stem cells and their progeny. In addition, exogenous Tβ4 increases the rate of hair growth in mice and promotes cashmere production by increasing the number of secondary HFs (hair follicles) in cashmere goats. However, the molecular mechanisms through which Tβ4 promotes HF growth and development have rarely been reported. Herein, we review the functions and mechanisms of Tβ4 in HF growth and development and describe the endogenous and exogenous actions of Tβ4 in HFs to provide insights into the roles of Tβ4 in HF growth and development.

Expression and localization of Sox10 during hair follicle morphogenesis and induced hair cycle.

Sox transcription factors play many diverse roles during development, including regulating stem cell states, directing differentiation, and influencing the local chromatin landscape. Sox10 has been implicated in the control of stem/progenitor activity and epithelial-mesenchymal transition, yet it has not been studied in relation to the hair follicle cycle or hair follicle stem cell (HFSC) control. To elucidate the role of Sox10 in hair follicle cycle control, we performed immunohistochemical and immunofluorescence analysis of its expression during hair morphogenesis, the postnatal hair cycle, and the depilation-induced murine hair follicle cycle. During hair follicle morphogenesis, Sox10 was expressed in the hair germ and peg. In telogen, we detected nuclear Sox10 in the hair bulge and germ cell cap, where HFSCs reside, while in anagen and catagen, Sox10 was detected in the epithelial portion, such as the strands of keratinocytes, the outer root sheath (ORS) in anagen, and the regressed epithelial strand of hair follicle in catagen. These results suggest that Sox10 may be involved in early hair follicle morphogenesis and postnatal follicular cycling.

Xenotransplantation of a Full-Layer Human Skin Strip as a Model for Studying Skin Regeneration and the Hair Follicle Cycle

Xenotransplantation of skin transplants from humans to animals with immunodeficiency is one of the most successful models for studying human tissues in normal and pathological conditions. The main limitation of this approach is the size of the graft; the lower part of the dermis and subcutaneous fat is missing in skin explants with an area of more than 10 × 10 mm, and full-layer xenografts rarely exceed the size of 3 × 3 mm. This study shows that transplantation of 15 × 5 mm full-layer strips ensures successful integration and preservation of all skin structures: the epidermis, dermal part, blood vessels, hair follicles, and sebaceous and sweat glands. Hair follicles in the grafts reproduce the cycle of physiological regeneration. This model is suitable for studying the regeneration of hair follicles, glands, interfollicular epidermis, and other skin structures.

Anagen Hair Follicles Transplanted into Mature Human Scars Remodel Fibrotic Tissue

Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation, let alone methods to remodel mature scars. Here, we took a unique approach inspired by how healthy hair‑bearing skin undergoes physiological remodeling during the regular cycling of hair follicles. In a pilot clinical study, we tested if anagen hair follicles transplanted into human scars can actively remodel fibrotic tissue, similar to how they remodel the healthy skin. We collected full‑thickness skin biopsies and compared the morphology and transcriptional signature of fibrotic tissue before and after transplantation. We found that anagen hair follicles induced an increase in the epidermal thickness, interdigitation of the epidermal‑dermal junction, dermal cell density, and vessel density. Remodeling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibers, and their alignment. Consistent with these morphological changes, we found a shift in the cytokine milieu of scars with a long-lasting inhibition of pro‑fibrotic factors TGF‑β1, IL‑13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing therapeutic approaches to remodel mature scars.

The Potential of Fibroblast Growth Factors to Stimulate Hair Growth In Vitro

There is a great need for studying mechanisms of hair follicle cycles and designing small molecular drugs, biologics, formulation, and surgical treatment for androgenic alopecia (AGA, a common form of hair recession). While minoxidil has served as a solution in the past, it is a vasodilator and can react heavily with alcohol. Furthermore, minoxidil must be used at night, as it requires 6 hours for the product to settle and perform its function. Therefore, alternative approaches are needed to treat AGA. Numerous clinical trials are studying the use of fibroblast growth factors (FGFs) for tissue regeneration applications. Additionally, FGFs have been proven to stimulate stem cell growth and tissue regeneration. In the present study, we tested the effects of four FGFs, namely FGF1 (aFGF), FGF2 (bFGF), FGF10 (KGF-2), and FGF21, as compared to the gold standard, minoxidil, on isolated primary mouse hair follicle dermal papilla (DP) cells. We also used plain cell culture media (without growth factors or serum) as a negative control. Cell proliferation and viability were measured using both a biochemical assay and fluorescent microscope examinations. Our results indicate that several FGFs can promote DP cell proliferation. Interestingly, our results show that minoxidil promotes DP cell proliferation in the absence of a vascular system. In addition, DP cells cultured in FGFs exhibited a more organized cytoskeleton as compared to the ones cultured with minoxidil, suggesting the potential advantages of FGFs in general cellular health. In that regard, we hypothesize that FGFs can stimulate hair growth and treat AGA.

Characterization and functional analysis of SMAD2 regulation in hair follicle cycle in Angora rabbits.

Hair follicle (HF) development is characterized by periodic growth cycles regulated by numerous factors. We previously showed that SMAD2 might be involved in the HF growth cycle in Angora rabbits. However, its extra role in the HF growth and development remains obscure. In this study, we cloned the complete coding sequence (CDS) of the Angora rabbit SMAD2 gene. Within SMAD2 CDS, we identified the open reading frame (ORF) had a length of 1314bp and encoding 437 amino acids. Bioinformatics analyses revealed that the SMAD2 protein is unstable and hydrophilic, and predominatelylocalizesin the cell nucleus. We identified that SMAD2 expression was elevated in the telogen phase of the during HF cycle. The knockdown and overexpression of SMAD2 could regulate HF growth and development related genes, such as WNT2, FGF2, and LEF1.Furthermore, SMAD2 may upregulate TGF-β signaling pathway-related genes, including TFDP1, E2F4, and RBL1. In conclusion, our results indicate that SMAD2 plays a vital role in HF development by regulating the TGF-β signaling pathway.

Diverse cellular players orchestrate regeneration after wounding.

Fibrosis is one of the largest sources of human morbidity. The skin is a complex organ where interplay between diverse cell types and signalling pathways is essential both in homeostasis and wound repair, which can result in fibrosis or regeneration. This makes skin a useful model to study fibrosis and regeneration. While fibrosis often occurs postinjury, both clinical and laboratory observations suggest skin regeneration, complete with reconstituted cell diversity and de novo hair follicles, is possible. Extensive research performed in pursuit of skin regeneration has elucidated the key players, both cellular and molecular. Interestingly, some cells known for their homeostatic function are not implicated in regeneration or wound-induced hair neogenesis (WIHN), suggesting regeneration harnesses separate functional pathways from embryogenesis or other non-homeostatic mechanisms. For example, classic bulge cells, noted for their role in normally cycling hair follicles, do not finally contribute to long-lived cells in the regenerated tissue. During healing, multiple populations of cells, among them specific epithelial lineages, mesenchymal cells, and immune cells promote regenerative outcomes in the wounded skin. Ultimately, targeting specific populations of cells will be essential in manipulating a postwound environment to favour regeneration in lieu of fibrosis.

Clues that mitochondria are involved in the hair cycle clock: MPZL3 regulates entry into and progression of murine hair follicle cycling.

The molecular nature of the hair cycle clock (HCC), the intrinsic oscillator system that drives hair follicle (HF) cycling, remains incompletely understood; therefore, all relevant key players need to be identified. Here, we present evidence that implicates myelin protein zero-like 3 (MPZL3), a multifunctional nuclear-encoded mitochondrial protein known to be involved in epidermal differentiation, in HCC regulation. By analysing global Mpzl3 knockout (-/-) mice, we show that in the absence of functional MPZL3, mice commence HF cycling with retarded first catagen-telogen transition after normal postnatal HF morphogenesis. However, Mpzl3 -/- mice subsequently display strikingly accelerated HF cycling, i.e. a precocious telogen-to-anagen transition during the second hair cycle, compared to controls, suggesting that MPZL3 inhibits anagen entry. We also show that intrafollicular MPZL3 protein expression fluctuates in a hair cycle-dependent manner. In telogen HFs, MPZL3 is localized to the secondary hair germ, an epicentre of hair cycle regulation, where it partially co-localizes with P-cadherin. In early anagen HF, MPZL3 is localized immediately distal to the proximal hair matrix. These findings introduce the novel concept that mitochondria are more actively involved in hair cycle control than previously recognized and that MPZL3 plays a central role in the HCC.

Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation.

There are many studies devoted to the role of hair follicle stem cells in wound healing as well as in follicle self-restoration. At the same time, the influence of the inflammatory cells on the hair follicle cycling in both injured and intact skin is well established. Immune cells of all wound healing stages, including macrophages, γδT cells, and Tregs, may activate epidermal stem cells to provide re-epithelization and wound-induced hair follicle neogenesis. In addition to the ability of epidermal cells to maintain epidermal morphogenesis through differentiation program, they can undergo de-differentiation and acquire stem features under the influence of inflammatory milieu. Simultaneously, a stem cell compartment may undergo re-programming to adopt another fate. The proportion of skin resident immune cells and wound-attracted inflammatory cells (e.g., neutrophils and macrophages) in wound-induced hair follicle anagen and plucking-induced anagen is still under discussion to date. Experimental data suggesting the role of reactive oxygen species and prostaglandins, which are uncharacteristic of the intact skin, in the hair follicle cycling indicates the role of neutrophils in injury-induced conditions. In this review, we discuss some of the hair follicles stem cell activities, such as wound-induced hair follicle neogenesis, hair follicle cycling, and re-epithelization, through the prism of inflammation. The plasticity of epidermal stem cells under the influence of inflammatory microenvironment is considered. The relationship between inflammation, scarring, and follicle neogenesis as an indicator of complete wound healing is also highlighted. Taking into consideration the available data, we also conclude that there may exist a presumptive interlink between the stem cell activation, inflammation and the components of programmed cell death pathways.

Wound Induced Hair Neogenesis - A Novel Paradigm for Studying Regeneration and Aging.

Hair follicles are the signature dermal appendage of mammals. They can be thought of as mini-organs with defined polarity, distinct constituent cell types, dedicated neurovascular supply, and specific stem cell compartments. Strikingly, some mammals show a capacity for adult hair follicle regeneration in a phenomenon known as wound-induced hair neogenesis (WIHN). In WIHN functional hair follicles reemerge during healing of large cutaneous wounds, and they can be counted to provide an index of regeneration. While age-related decline in hair follicle number and cycling are widely appreciated in normal physiology, it is less clear whether hair follicle regeneration also diminishes with age. WIHN provides an extraordinary quantitative system to address questions of mammalian regeneration and aging. Here we review cellular and molecular underpinnings of WIHN, explore known age-related changes to these elements, and present unanswered questions for future exploration.

Examination of androgenetic alopecia with serum biomarkers.

Androgenetic alopecia (AGA) is the most common type of hair loss and affects approximately 50% of the male population. In the present study, to investigate microinflammation, perifollicular fibrosis, and oxidative stress in AGA cases, some serum biomarker levels were measured and evaluated. Serum samples were drawn from patients (n=58) and control (n=30) groups referring to Atatürk Training and Investigation Hospital Dermatology Outpatient clinic. In serum samples, NF-κB, TNF-α, TGF-β1, thioredoxin, nitric oxide, TOS, TAS, and thiol disulfide homeostasis (native thiol, total thiol, disulfide) were measured and evaluated. In patients with AGA, NF-κB (P=.005), TNF-α (P=.008), TGF-β1 (P=.028), thioredoxin (P=.004), nitric oxide (P<.001), and TOS (P<.001) serum levels were found to be significantly higher than those in control group, while TAS (P=.003), native thiol (P<.001), total thiol (P<.001), and disulfide (P<.001) serum levels were found to be significantly lower. According to the results of the present study, it was concluded that in that AGA androgens lead to oxidative stress by increasing free oxygen radicals, which accelerates hair loss by causing microinflammation and fibrosis. The recognition of the effect of androgens and associated factors on the hair follicle cycle is essential for the development of new and effective treatment methods.

Genome-wide detection and sequence conservation analysis of long non-coding RNA during hair follicle cycle of yak

BackgroundLong non-coding RNA (lncRNA) as an important regulator has been demonstrated playing an indispensable role in the biological process of hair follicles (HFs) growth. However, their function and expression profile in the HFs cycle of yak are yet unknown. Only a few functional lncRNAs have been identified, partly due to the low sequence conservation and lack of identified conserved properties in lncRNAs. Here, lncRNA-seq was employed to detect the expression profile of lncRNAs during the HFs cycle of yak, and the sequence conservation of two datasets between yak and cashmere goat during the HFs cycle was analyzed.ResultsA total of 2884 lncRNAs were identified in 5 phases (Jan., Mar., Jun., Aug., and Oct.) during the HFs cycle of yak. Then, differential expression analysis between 3 phases (Jan., Mar., and Oct.) was performed, revealing that 198 differentially expressed lncRNAs (DELs) were obtained in the Oct.-vs-Jan. group, 280 DELs were obtained in the Jan.-vs-Mar. group, and 340 DELs were obtained in the Mar.-vs-Oct. group. Subsequently, the nearest genes of lncRNAs were searched as the potential target genes and used to explore the function of DELs by GO and KEGG enrichment analysis. Several critical pathways involved in HFs development such as Wnt signaling pathway, VEGF signaling pathway, and signaling pathways regulating pluripotency of stem cells, were enriched. To further screen key lncRNAs influencing the HFs cycle, 24 DELs with differ degree of sequence conservation were obtained via a comparative analysis of partial DELs with previously published lncRNA-seq data of cashmere goat in the HFs cycle using NCBI BLAST-2.9.0+, and 3 DELs of them were randomly selected for further detailed analysis of the sequence conservation properties.ConclusionsThis study revealed the expression pattern and potential function of lncRNAs during HFs cycle of yak, which would expand the knowledge about the role of lncRNAs in the HFs cycle. The findings related to sequence conservation properties of lncRNAs in the HFs cycle between the two species may provide valuable insights into the study of lncRNA functionality and mechanism.

Hair follicle regional specificity in different parts of bay Mongolian horse by histology and transcriptional profiling

BackgroundDifferent morphological structures of hairs having properties like defense and camouflage help animals survive in the wild environment. Horse is one of the rare kinds of animals with complex hair phenotypes in one individual; however, knowledge of horse hair follicle is limited in literature and their molecular basis remains unclear. Therefore, the investigation of horse hair follicle morphogenesis and pigmentogenesis attracts considerable interest.ResultHistological studies revealed the morphology and pigment synthesis of hair follicles are different in between four different parts (mane, dorsal part, tail, and fetlock) of the bay Mongolian horse. Hair follicle size, density, and cycle are strongly associated with the activity of alkaline phosphatase (ALP). We observed a great difference in gene expression between the mane, tail, and fetlock, which had a greater different gene expression pattern compared with the dorsal part through transcriptomics. The development of the hair follicle in all four parts was related to angiogenesis, stem cells, Wnt, and IGF signaling pathways. Pigmentogenesis-related pathways were involved in their hair follicle pigment synthesis.ConclusionsHair follicle morphology and the activity of ALP differ among four body parts in bay Mongolian horse. Hair follicles of the different body parts of the are not synchronized in their cycle stages. GO terms show a regional specificity pattern between different skin parts of the bay Mongolian horse. These results provide an insight into the understanding of the biological mechanism of the hair follicle in other mammals.

Hormonal Effects on Hair Follicles.

The hair cycle and hair follicle structure are highly affected by various hormones. Androgens—such as testosterone (T); dihydrotestosterone (DHT); and their prohormones, dehydroepiandrosterone sulfate (DHEAS) and androstendione (A)—are the key factors in terminal hair growth. They act on sex-specific areas of the body, converting small, straight, fair vellus hairs into larger darker terminal hairs. They bind to intracellular androgen receptors in the dermal papilla cells of the hair follicle. The majority of hair follicles also require the intracellular enzyme 5-alpha reductase to convert testosterone into DHT. Apart from androgens, the role of other hormones is also currently being researched—e.g., estradiol can significantly alter the hair follicle growth and cycle by binding to estrogen receptors and influencing aromatase activity, which is responsible for converting androgen into estrogen (E2). Progesterone, at the level of the hair follicle, decreases the conversion of testosterone into DHT. The influence of prolactin (PRL) on hair growth has also been intensively investigated, and PRL and PRL receptors were detected in human scalp skin. Our review includes results from many analyses and provides a comprehensive up-to-date understanding of the subject of the effects of hormonal changes on the hair follicle.

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.

SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice

Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life‐cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen‐to‐anagen transition, and HFSC‐specific Sirt7 knockout mice (Sirt7f/f;K15‐Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ‐dependent proteasomal degradation to terminate Nfatc1‐mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7−/− mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.

Transcriptome-based selection and validation of optimal house-keeping genes for skin research in goats (Capra hircus)

BackgroundIn quantitative real-time polymerase chain reaction (qRT-PCR) experiments, accurate and reliable target gene expression results are dependent on optimal amplification of house-keeping genes (HKGs). RNA-seq technology offers a novel approach to detect new HKGs with improved stability. Goat (Capra hircus) is an economically important livestock species and plays an indispensable role in the world animal fiber and meat industry. Unfortunately, uniform and reliable HKGs for skin research have not been identified in goat. Therefore, this study seeks to identify a set of stable HKGs for the skin tissue of C. hircus using high-throughput sequencing technology.ResultsBased on the transcriptome dataset of 39 goat skin tissue samples, 8 genes (SRP68, NCBP3, RRAGA, EIF4H, CTBP2, PTPRA, CNBP, and EEF2) with relatively stable expression levels were identified and selected as new candidate HKGs. Commonly used HKGs including SDHA and YWHAZ from a previous study, and 2 conventional genes (ACTB and GAPDH) were also examined. Four different experimental variables: (1) different development stages, (2) hair follicle cycle stages, (3) breeds, and (4) sampling sites were used for determination and validation. Four algorithms (geNorm, NormFinder, BestKeeper, and ΔCt method) and a comprehensive algorithm (ComprFinder, developed in-house) were used to assess the stability of each HKG. It was shown that NCBP3 + SDHA + PTPRA were more stably expressed than previously used genes in all conditions analysis, and that this combination was effective at normalizing target gene expression. Moreover, a new algorithm for comprehensive analysis, ComprFinder, was developed and released.ConclusionThis study presents the first list of candidate HKGs for C. hircus skin tissues based on an RNA-seq dataset. We propose that the NCBP3 + SDHA + PTPRA combination could be regarded as a triplet set of HKGs in skin molecular biology experiments in C. hircus and other closely related species. In addition, we also encourage researchers who perform candidate HKG evaluations and who require comprehensive analysis to adopt our new algorithm, ComprFinder.

Transient stimulation of TRPV4-expressing keratinocytes promotes hair follicle regeneration in mice.

Hair follicle telogen to anagen transition results in a break in cellular quiescence of the hair follicle stem cells, which subsequently promotes hair follicle regeneration. Many critical molecules and signalling pathways are involved in hair follicle cycle progression. Transient receptor potential vanilloid 4 (TRPV4) is a polymodal sensory transducer that regulates various cutaneous functions under both normal and disease conditions. However, the role of TRPV4 in hair follicle regeneration in vivo remains incompletely understood. Using adult C57BL/6J mice, keratinocyte (K14Cre ; Trpv4f/f ) and macrophage (Cx3cr1Cre ; Trpv4f/f ) Trpv4 conditional knockout (cKO) mice, Trpv4-/- mice, we investigated the effect of a single intradermal injection of GSK1016790A, a potent and selective small molecule TRPV4 activator, on hair follicle regeneration. Chemical cues and signal molecules involved in hair follicle cycle progression were measured by immunofluorescence staining, quantitative RT-PCR and western blotting. Here, we show that a single intradermal injection of GSK1016790A is sufficient to induce telogen to anagen transition and hair follicle regeneration in mice by increasing the expression of the anagen-promoting growth factors and down-regulating the expression of growth factors that inhibit anagen. The action of GSK1016790A relies largely on the function of TRPV4 in skin and involves activation of downstream ERK signalling. Our results suggest that transient chemical activation of TRPV4 in the skin induces hair follicle regeneration in mice, which might provide an effective therapeutic strategy for the treatment of hair loss and alopecia.

The effect of hypoxia on the proliferation capacity of dermal papilla cell by regulating lactate dehydrogenase.

Hypoxia is of great significance for stem cells to maintain the proliferation and differentiation capacity. As a specialized mesenchymal component of the hair follicle (HF), the dermal papilla cell (DPC) not only regulates HF cycle, but also plays a pivotal role in differentiating hair follicle stem cell(HFSC) into HF. However, whether hypoxia could affect DPCs on proliferation or metabolism remains unclear. In our study, DPCs were cultured in normoxia (20%O2) or hypoxia (5%O2). Cell viability assays were performed, and lactate dehydrogenase (LDH) activity and lactate level in DPCs were detected. After that, LDH was overexpressed or knocked down in DPCs; then, the expression of protein markers (ALP, Ki‐67) was assessed by Western blotting, and cell proliferation was also detected after overexpression or knockdown of LDH. Hypoxia did show positive effect on proliferation of DPCs. The LDH activity of DPCs cultured under hypoxic condition was significantly higher than that of cultured under normoxic condition. Overexpression of LDH significantly up‐regulates the expression of ALP and Ki‐67 compared with knockdown and negative control. Cell proliferation was also promoted in DPCs with elevated LDH. Our findings showed that the proliferation activity of DPCs could be stimulated under hypoxia. Meanwhile, LDH plays an important role in maintaining the activity of DPCs in hypoxic condition.