• 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.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.545-550
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• 2021

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.5.1-5.15
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• 2018

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.

• Molecules and Cells
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• v.46 no.10
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• pp.573-578
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• 2023

The mammalian skin contains hair follicles, which are epidermal appendages that undergo periodic cycles and exhibit mini-organ features, such as discrete stem cell compartments and different cellular components. Wound-induced hair follicle neogenesis (WIHN) is the remarkable ability to regenerate hair follicles after large-scale wounding and occurs in several adult mammals. WIHN is comparable to embryonic hair follicle development in its processes. Researchers are beginning to identify the stem cells that, in response to wounding, develop into neogenic hair follicles, as well as to understand the functions of immune cells, mesenchymal cells, and several signaling pathways that are essential for this process. WIHN represents a promising therapeutic approach to the reprogramming of cellular states for promoting hair follicle regeneration and preventing scar formation. In the scope of this review, we investigate the contribution of several cell types and molecular mechanisms to WIHN.

• 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.

• BMB Reports
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• v.56 no.1
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• pp.2-9
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• 2023

Hair follicles in the skin undergo cyclic rounds of regeneration, degeneration, and rest throughout life. Stem cells residing in hair follicles play a pivotal role in maintaining tissue homeostasis and hair growth cycles. Research on hair follicle aging and age-related hair loss has demonstrated that a decline in hair follicle stem cell (HFSC) activity with aging can decrease the regeneration capacity of hair follicles. This review summarizes our understanding of how age-associated HFSC intrinsic and extrinsic mechanisms can induce HFSC aging and hair loss. In addition, we discuss approaches developed to attenuate ageassociated changes in HFSCs and their niches, thereby promoting hair regrowth.

• The Journal of Korean Institute of Communications and Information Sciences
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• v.21 no.5
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• pp.1304-1316
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• 1996

In this paper, A VCO(Voltage Controlled Oscillator) in use of clock recovery/data regeneration circuit for 10 Gbps fiber optic receivers was developed. The improved hair-pin resonator with a parallel coupled lines, which has been applied to microstrip filters, was used as a resonance part. As a frequcncy tuning device by substituting 3-terminalMESFET vaaractor for varactor diode, an MMIC manufacturing process will be simplified. Since a hair-pin resonator is planar type compared to the dielectric resonator and has a relatively flat reactance verus frequency, it will be favorable to apply a hair-pin resonator to an MMIC, in addition wideband frequency tuning range is able to be obtained.

• Journal of dental hygiene science
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• v.23 no.4
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• pp.369-377
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• 2023

Background: In this study, we investigated the potential use of keratin for oral tissue regeneration. Keratin is well-known for its effectiveness in skin regeneration by promoting keratinization and enhancing the elasticity and activity of fibroblasts. Because of its structural stability, high storability, biocompatibility, and safety in humans, existing research has predominantly focused on its role in skin wound healing. Herein, we propose using keratin proteins as biocompatible materials for dental applications. Methods: To assess the suitability of alpha-keratin protein as a substrate for cell culture, keratin was extracted from human hair via PEGylation. Viabilities of primary human gingival fibroblasts (HGFs) and human oral keratinocytes (HOKs) were assessed. Fluorescence immunostaining and migration assays were conducted using a fluorescence microscope and confocal laser scanning microscope. Wound healing and migration assays were performed using automated software to analyze the experimental readout and gap closure rate. Results: We confirmed the extraction of alpha-keratin and formation of the PEG-g-keratin complex. Treatment of HGFs with keratin protein at a concentration of 5 mg/ml promoted proliferation and maintained cell viability in the test group compared to the control group. HOKs treated with 5 mg/ml keratin exhibited a slight decrease in cell proliferation and activity after 48 hours compared to the untreated group, followed by an increase after 72 hours. Wound healing and migration assays revealed rapid closure of the area covered by HOKs over time following keratin treatment. Additionally, HOKs exhibited changes in cell morphology and increased the expression of the mesenchymal marker vimentin. Conclusion: Our study demonstrated the potential of hair keratin for soft tissue regeneration, with potential future applications in clinical settings for wound healing.

• BMB Reports
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• v.55 no.11
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• pp.559-564
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• 2022

Diabetes mellitus is one of the most prevalent diseases in modern society. Many complicationssuch as hepatic cirrhosis, neuropathy, cardiac infarction, and so on are associated with diabetes. Although a relationship between diabetes and hair loss has been recently reported, the treatment of diabetic hair loss by Wnt/β-catenin activators has not been achieved yet. In this study, we found that the depilation-induced anagen phase was delayed in both db/db mice and high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice. In diabetic mice, both hair regrowth and wound-induced hair follicle neogenesis (WIHN) were reduced because of suppression of Wnt/β-catenin signaling and decreased proliferation of hair follicle cells. We identified that KY19382, a small molecule that activates Wnt/β-catenin signaling, restored the capabilities of regrowth and WIHN in diabetic mice. The Wnt/β-catenin signaling activator also increased the length of the human hair follicle which was decreased under high glucose culture conditions. Overall, the diabetic condition reduced both hair regrowth and regeneration with suppression of the Wnt/β-catenin signaling pathway. Consequently, the usage of Wnt/β-catenin signaling activators could be a potential strategy to treat diabetes-induced alopecia patients.

• Korean Journal of Pharmacognosy
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• v.44 no.3
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• pp.275-280
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• 2013

This study was carried out to investigate the effect of Origanum vulgare extracts on cell proliferation of human hair dermal papilla cell (HHDPC) using sulforhodamine B (SRB) assay, antioxidant activity by 1,1-diphenyl-2-picryl hydrazyl (DPPH) method, expression of insulin-like growth factor-1 (IGF-1) by analyzing reverse transcriptase polymerase chain reaction (RT-PCR) and hair growth in a shaving animal model of C57BL/6 mice topically applying with an amount of 0.1 mL once a day for 3 weeks. The mice were divided into 4 groups including normal group (saline, N), negative control group (dimethyl sulfoxide, NC), positive control group (5 mg/mL minoxidil, PC), and experimental group (Origanum vulgare extracts, OV). Treatment of OV didn't show cytotoxicity in HHDPC up to 10 ${\mu}g/mL$ and exhibited antioxidant activity with $IC_{50}$ of 31.0 ${\mu}g/mL$. IGF-1 expression in the skin was significantly (p<0.05) increased in the PC and OV compared to the N or NC. PC and OV also showed a prominently promoted hair regrowth compared to the N or NC in hair growth observation. The hair regrowth of OV was significantly higher than that of PC (p<0.05). Therefore, these results indicate that O. vulgare extracts effectively stimulated hair growth in an animal model.