• BMB Reports
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• v.45 no.4
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• pp.253-258
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• 2012

The dermal papilla cells (DPCs) of hair follicles are known to secrete paracrine factors for follicular cells. Shotgun proteomic analysis was performed to compare the expression profiles of the secretomes of human DPCs and dermal fibroblasts (DFs). In this study, the proteins secreted by DPCs and matched DFs were analyzed by 1DE/LTQ FTICR MS/MS, semi-quantitatively determined using emPAI mole percent values and then characterized using protein interaction network analysis. Among the 1,271 and 1,188 proteins identified in DFs and DPCs, respectively, 1,529 were further analyzed using the Ingenuity Pathway Analysis tool. We identified 28 DPC-specific extracellular matrix proteins including transporters (ECM1, A2M), enzymes (LOX, PON2), and peptidases (C3, C1R). The biochemically-validated DPC-specific proteins included thrombospondin 1 (THBS1), an insulin-like growth factor binding protein3 (IGFBP3), and, of particular interest, an integrin beta1 subunit (ITGB1) as a key network core protein. Using the shotgun proteomic technique and network analysis, we selected ITGB1, IGFBP3, and THBS1 as being possible hair-growth modulating protein biomarkers.

• Food Science of Animal Resources
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• v.44 no.1
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• pp.204-215
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• 2024

This study was designed to examine the effect of Lactilactobacillus curvatus LB-P9 on hair regeneration. The treatment of LB-P9 conditioned medium increased the proliferation of both hair follicle dermal papilla cells and hair germinal matrix cells (hGMCs). Moreover, the expression levels of hair growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 7 were significantly elevated in hGMCs co-cultured with LB-P9. After time-synchronized depilation, mice were orally administered with either 4×10⁷ colony forming unit (CFU) of LB-P9 (low dose) or 4×10⁸ CFU of LB-P9 (high dose), once daily for 4 weeks. Compared with the vehicle (phosphate-buffered saline)-administrated group, the LB-P9-treated groups exhibited accelerated hair regrowth rate and enhanced hair thickness in a dose-dependent manner. Supporting this observation, both hair follicle numbers and the dermal thickness in skin tissues of the LB-P9-treated groups were increased, compared to those of the vehicle-treated group. These results might be explained by the increased level of β-catenin and number of hair follicle stem cells (CD34⁺ CD49f⁺ cells) in the skin tissues of mice administered with LB-P9, compared to the vehicle-treated mice. Also, increased serum levels of hair growth factors such as VEGF and insulin-like growth factor-1, and superoxide dismutase were found in the LB-P9-treated groups, compared to those of the vehicle-treated group. Taken together, these results might demonstrate that the oral administration of LB-P9 promotes hair regeneration by the enhancement of dermal papilla proliferation through the stimulation of hair growth factor production.

• Korean Journal of Pharmacognosy
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• v.48 no.3
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• pp.195-201
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• 2017

To develop new therapy for prevention and treatment of hair loss is very important according to increase of the number of hair loss people. The aim of this study was to investigate the hair growth promoting effects of pectin lyase-modified red ginseng extract (GS-E3D). We examined antioxidant and anti-inflammatory effects, human hair dermal papilla cells (HHDPC) proliferation, and testoterone-induced $5{\alpha}$-reductase inhibitory effects. GS-E3D show not only 1,1-diphenyl-2-picryhydrazyl (DPPH) radical scavenging activity and xanthine oxidase inhibitory effects as an anti-oxidant property, but also lip-oxygenase and hyaluronidase inhibitory effects as an anti-inflammatory property. Human hair dermal papilla cells proliferation by GS-E3D was higher than those of minoxidil or finasteride, using the positive controls. Moreover, GS-E3D exhibited $5{\alpha}$-reductase inhibitory activities after stimulating by testoterone. The present results indicate that GS-E3D has a potential to be as an hair growth promoting agent for cosmetic materials.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.3
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• pp.167-172
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• 2017

In this study, we investigated the effect of Puerariae Radix ethanol extracts (EPR). The effect of the EPR on proliferation of human hair dermal papilla cells(HHDPCs) by MTT assay and observed Expression of mechanisms that regulate cell proliferation extracellular signal-regulated kinase(ERK) and Akt by western blot. The results showed EPR increased the proliferation of HHDPCs and up-regulation phosphorylation of ERK and Akt. ERK and Akt increased by EPR inhibited phosphorylation by PD98059 (ERK inhibitor) and LY294002 (Akt inhibitor), and cell proliferation was also inhibited. These results suggested EPR increases the proliferation of HHDPCs through phosphorylation of ERK and Akt, and therefore is a beneficial effect for the alopecia treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.6
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• pp.374-379
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• 2017

Hair loss affects interpersonal relationships and causes psychological stress. In this study, we investigated the antioxidant activity of Cynanchi Wilfordii Radix (CWR) and its effects on dermal papilla (DP) cells. Antioxidant efficacy was examined by ABTS assay. To confirm the effect on cell activity, MTS assay was performed and cell count was directly measured by hemocytometer. The mRNA expression of genes involved in hair formation and hair loss formation was confirmed by quantitative RT-PCR. CWR has a strong antioxidant activity. Cell viability of DP cells was increased to 118.5% by treatment of 0.5 mg/ml CWR for 24 hours, but the effect on the cell number was insignificant. These results suggest that CWR increases mitochondrial activity without promoting cell proliferation. Treatment of DP cells with 0.5 mg/ml CWR resulted in 48.5% reduction of mRNA expression of type 2 $5{\alpha}$-reductase, a major cause of male hair loss. In addition, mRNA expression of bone morphogenetic pretein (BMP), fibroblast growth factor (FGF)7, and FGF10, which are closely related to hair growth, was also decreased. Reactive oxygen species (ROS) acts as a cause of hair loss. The excellent antioxidant efficacy of CWR is thought to be able to effectively remove ROS. The dihydrotestosterone produced by type 2 $5{\alpha}$-reductase in DP cells is a potent inducer of male pattern hair loss. The inhibitory effect of type 2 $5{\alpha}$-reductase mRNA on DP cells induced by CWR may induce a positive therapeutic effect of male pattern hair loss.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.354-360
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• 2020

The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)-Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)-glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.43-51
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• 2022

Regulation of the hair follicle cycle in association with dermal papilla cells is one of the most interesting targets for promoting hair regrowth. In this study, we examined whether steam-dried Betula platyphylla extracts (BPE) promote hair growth by upregulating in vitro and in vivo responses of dermal papilla cells. The data showed that BPE3 contained high amounts of phenolic compounds with higher antioxidant effects and increased hair growth-related genes, including fibroblast growth factor7 and Wnt7b, in dermal papilla cells. Notably, BPE3 effectively enhanced the formation of hair follicles by increasing FGF7, Wnt7b, and vascular endothelial growth factor in C57BL/6N dorsal skins. Additionally, BPE3 significantly decreased the expression of inflammatory repertoires, inducible nitric oxide synthase, interleukin-6, and cyclooxygenase 2. Several small molecules, such as betulin and unsaturated fatty acids, support the pharmacological activity of BPE3. In conclusion, BPE3 effectively promoted hair growth by activating dermal papilla cells and enhancing hair follicle cycles by attenuating the inflammatory environment in the scalp.

• Development and Reproduction
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• v.25 no.4
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• pp.279-291
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• 2021

Hair loss is one of the most common chronic diseases, with a detrimental effect on a patient's psychosocial life. Hair loss results from damage to the hair follicle (HF) and/or hair regeneration cycle. Various damaging factors, such as hereditary, inflammation, and aging, impair hair regeneration by inhibiting the activation of hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Formyl peptide receptor 2 (FPR2) regulates the inflammatory response and the activity of various types of stem cells, and has recently been reported to have a protective effect on hair loss. Given that stem cell activity is the driving force for hair regeneration, we hypothesized that FPR2 influences hair regeneration by mediating HFSC activity. To prove this hypothesis, we investigated the role of FPR2 in hair regeneration using Fpr2 knockout (KO) mice. Fpr2 KO mice were found to have excessive hair loss and abnormal HF structures and skin layer construction compared to wild-type (WT) mice. The levels of Sonic hedgehog (Shh) and β-catenin, which promote HF regeneration, were significantly decreased, and the expression of bone morphogenetic protein (Bmp)2/4, an inhibitor of the anagen phase, was significantly increased in Fpr2 KO mice compared to WT mice. The proliferation of HFSCs and DPCs was significantly lower in Fpr2 KO mice than in WT mice. These findings demonstrate that FPR2 impacts signaling molecules that regulate HF regeneration, and is involved in the proliferation of HFSCs and DPCs, exerting a protective effect on hair loss.

• Journal of Life Science
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• v.27 no.11
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• pp.1269-1275
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• 2017

Tenebrio molitor samples were investigated as novel biomaterials and sources of food in several recent studies. However, the insects' effects on hair growth were not sufficiently researched. To develop novel and natural materials for preventing alopecia and promoting hair growth, this study investigated the antioxidant activities and hair-growth promotion effects of TMEs. To determine the antioxidant activities, the TMEs' DPPH radical- and nitrite-scavenging activities were examined. To determine hair-growth promotion effects, proliferations of human dermal papilla cells (DPCs) and the murine fibroblast cell line NIH3T3 were evaluated by using an MTS assay. In addition, estimations were made for cell viabilities against cell death induced by dihydrotesterone (DHT) in DPCs and inhibitory effects against potassium channel blocking induced by tolbutamide (TBM) in NIH3T3 cells. The DPPH radical scavenging activity was 81.17%, and the nitrite scavenging activity was 43.69%; the activities were similar to the activities of blueberry extracts. Moreover, the TMEs promoted the proliferation of human DPCs and NIH3T3 cells, which were concentrated dependently. The TMEs prevented not only DHT-induced DPC cytotoxicity but also TBM's action as a potassium channel blocker in NIH3T3 cells. The results suggested that TME could be used as a functional therapeutic alopecia reagent, to prevent hair loss and to promote hair growth.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.174-179
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• 2015

BP201, porcine lung tissue-derived phospholipids, consists of phosphatidylcholine as a major phospholipid species. BP201 promoted hair growth after application onto the shaved backs of BALB/c and C3H mice. Its effect was enhanced when applied together with minoxidil (MNX) in C3H mice. When the tissue specimens prepared from the shaved skins of BP201-treated and control mice were microscopically examined, the total numbers of hair follicles in both anagen and telogen phases of BP201-treated mice were significantly higher than those of control mice. The numbers of hair follicles in the anagen phase of BP201-treated mice were also higher than those of control mice. In combination with MNX, BP201 further increased the total number of hair follicles, but did not alter the percentage of hair follicles in the anagenic phase. BP201 also increased the proliferation of human hair follicle dermal papilla cells. Collectively, BP201 possesses hair growth promoting potential, which would suggest its use singly or in combination for hair growth products.