• Journal of Ginseng Research
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• v.47 no.3
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• pp.440-447
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• 2023

Background: The human hair follicle undergoes cyclic phases-anagen, catagen, and telogen-throughout its lifetime. This cyclic transition has been studied as a target for treating hair loss. Recently, correlation between the inhibition of autophagy and acceleration of the catagen phase in human hair follicles was investigated. However, the role of autophagy in human dermal papilla cells (hDPCs), which is involved in the development and growth of hair follicles, is not known. We hypothesized that acceleration of hair catagen phase upon inhibition of autophagy is due to the downregulation of Wnt/β-catenin signaling in hDPCs, and that components of Panax ginseng extract can increase the autophagic flux in hDPCs. Methods: We generated an autophagy-inhibited condition using 3-methyladenine (3-MA), a specific autophagy inhibitor, and investigated the regulation of Wnt/β-catenin signaling using the luciferase reporter assay, qRT-PCR, and western blot analysis. In addition, cells were cotreated with ginsenoside Re and 3-MA and their roles in inhibiting autophagosome formation were investigated. Results: We found that the unstimulated anagen phase dermal papilla region expressed the autophagy marker, LC3. Transcription of Wnt-related genes and nuclear translocation of β-catenin were reduced after treatment of hDPCs with 3-MA. In addition, treatment with the combination of ginsenoside Re and 3-MA changed the Wnt activity and hair cycle by restoring autophagy. Conclusions: Our results suggest that autophagy inhibition in hDPCs accelerates the catagen phase by downregulating Wnt/β-catenin signaling. Furthermore, ginsenoside Re, which increased autophagy in hDPCs, could be useful for reducing hair loss caused by abnormal inhibition of autophagy.

• BMB Reports
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• v.44 no.8
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• pp.512-516
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• 2011

Establishment of immortalized human dermal papilla cells (DPCs) retaining the characteristics of DPCs would be a great help for hair researchers. We recently established a simian virus 40T (SV40T)-transformed human DP cell line (SV40TDPC). However, the cell line senesced around passage 25 and ceased proliferation. In this study, we introduced the human telomerase reverse transcriptase (hTERT) gene into SV40T-DPC and established an immortalized human DP cell line. The cell line, SV40T-hTERT-DPC, did not induce tumors when inoculated into nude mice. SV40T-hTERT-DPC maintained morphology of early passage DPCs, expressed markers of DPCs, and retained responses to Wnt/${\beta}$-catenin and bone morphogenic protein (BMP) signaling pathways known to be required for hair-inducing activity of DPCs. The data strongly suggest that SV40T-hTERT-DPC retains many characteristics of human DPCs in vivo without malignant transformation.

• Korean Journal of Acupuncture
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• v.34 no.3
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• pp.146-155
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• 2017

Objectives : This study was carried out to investigate the effects of Crataegi Fructus water extract(CFWE) on hair growth in an alopecia model of C57BL/6N mice and human dermal papilla cells(hDPCs). Methods : Six-week old mice were depilated and separated in 3 groups ; CON, MXD(2% Minoxidil), and CFWE. The treatments were applied twice a day for 18 days. The hair growth was determined photographically. The hair density, thickness and length were identified by Folliscope and the weights of body were measured. In dorsal skin tissue, the expression of hair growth-related protein was analyzed by Western blot. In hDPCs with/without $IFN-{\gamma}$, cell proliferation and the expression of hair growth-related genes were analyzed. Results : We observed that CFWE promoted hair growth compared to CON. CFWE improved the hair density, thickness and length compared to CON. CFWE increased the $Wnt/{\beta}$-catenin signaling in dorsal skin. In hDPCs, CFWE accelerated the cell proliferation and inhibited $IFN-{\gamma}$-induced hDPCs degeneration. CFWE increased the mRNA expression of ${\beta}$-catenin, Axin-2, BMP-4, FGF-7, FGF-10, and ALP compared to CON and $IFN-{\gamma}$ treated cells. Conclusions : These results suggest that CFWE has a hair regrowth activity via $Wnt/{\beta}$-catenin signaling and can be useful for the treatment of alopecia.

• Journal of Microbiology and Biotechnology
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• v.34 no.9
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• pp.1810-1818
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• 2024

Autophagy is essential for regulating hair growth. Accordingly, we developed autophagy activator ICP5249 (pentasodium tetracarboxymethyl palmitoyl dipeptide) and investigated its potential role in hair growth. We evaluated its effect on hair growth using in vitro human dermal papilla cells (hDPCs) culture model, human hair follicles (hHFs) organ culture model, and telogenic mouse model. ICP5249 increased hDPCs proliferation and alkaline phosphatase (ALP) expression. It also increased microtubule-associated protein (MAP) light chain 3-II (LC3-II) expression and AMP-activated protein kinase α (AMPKα) and unc-51-like kinase 1 (ULK1) phosphorylation in hDPCs. ICP5249 extended the length of hHFs and increased LC3-II please revised from LC3 II to LC3-II in all manuscript expression. Consistently, ICP5249 also significantly increased hair growth area, dermis thickness, and anagen and telogen ratio in telogenic mice. Furthermore, it upregulated Ki-67 and LC3-II expression and AMPKα phosphorylation on the mice's dorsal skin. To investigate whether AMPK regulates ICP5249-induced hair growth, following treatment with the compound C, AMPK inhibitor, the activity of ICP5249 was evaluated. The effects of ICP5249 on hair growth were assessed following pretreatment with the AMPK inhibitor compound C. The results showed that compound C suppressed ICP5249-mediated proliferation and hair inductivity in hDPCs. Additionally, compound C inhibited ICP5249-mediated hair growth area, dermis thickness, anagen and telogen ration, and LC3-II expression in mice, suggesting that ICP5249 promotes hair growth by modulating autophagy, with AMPKα playing a regulatory role in this process. Taken together, we demonstrate that ICP5249 has the potential as an ingredient for improving hair growth.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.640-646
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• 2024

Hair growth cycles are mainly regulated by human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). Protecting hDPCs from excessive oxidative stress and hORSCs from glycogen phosphorylase (PYGL) is crucial to maintaining the hair growth phase, anagen. In this study, we developed a new PYGL inhibitor, hydroxytrimethylpyridinyl methylindolecarboxamide (HTPI) and assessed its potential to prevent hair loss. HTPI reduced oxidative damage, preventing cell death and restored decreased level of anagen marker ALP and its related genes induced by hydrogen peroxide in hDPCs. Moreover, HTPI inhibited glycogen degradation and induced cell survival under glucose starvation in hORSCs. In ex-vivo culture, HTPI significantly enhanced hair growth compared to the control with minoxidil showing comparable results. Overall, these findings suggest that HTPI has significant potential as a therapeutic agent for the prevention and treatment of hair loss.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.555-566
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• 2018

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and ${\beta}-catenin$; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.4
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• pp.413-421
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• 2014

Corticotropin-releasing factor (CRF) is involved in the stress response and there is increasing evidence that stress influences skin disease such as hair loss. In cultured human hair follicles, CRF inhibits hair shaft elongation, induces premature regression and promotes the apoptosis of hair matrix keratinocytes. We investigated whether CRF influences the dermal papilla cells (DPC) that play pivotal roles in hair growth and cycling. Human DPCs were treated with CRF, adrenocorticotropic hormone (ACTH) and cortisol, key stress hormones along the hypothalamic-pituitary -adrenal (HPA) axis for 1-24 h. Interestingly, CRF modulated the expression of cytokines related to hair growth (KGF, Wnt5a, $TGF{\beta}-2$, Nexin) and increased cAMP production in cultured DPCs. CRF receptors were down-regulated by negative feedback systems. Pretreatment of CRF receptor antagonists or protein kinase A (PKA) inhibitor prevented the CRF-induced modulation. Since the CRF induces proopiomelanocortin (POMC) expression through the cAMP/PKA pathway, we analyzed POMC mRNA. CRF stimulated POMC expression in cultured human DPCs, yet we were unable to detect ACTH levels by western blot. These results indicate that CRF operates within DPCs through CRF receptors along the classical CRF signaling pathway and CRF receptor antagonists could serve as potential therapeutic and cosmetic agents for stress-induced hair loss.

• Microbiology and Biotechnology Letters
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• v.50 no.4
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• pp.533-547
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• 2022

This study investigated the hair growth effect of Schisandra chinensis extract (TS-SC) and TS-SC fermented by Lactobacillus plantarum (TS-SCLF) on human dermal papilla cells (hDPCs). The production of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), keratinocyte growth factor/fibroblast growth factor 7 (KGF/FGF-7) and hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-β1) were examined. The secretion rates of VEGF and KGF/FGF-7 were high in TS-SC, and the secretion rates of IGF-1 and HGF were high in TS-SCLF. TGF-β1 was inhibited in a concentration-dependent manner in all samples. Gene expression of VEGF, IGF-1, KGF, HGF and alkaline phosphatase, relevant to hair growth, were examined. The data revealed that TS-SC and TS-SCLF successfully promoted hair growth in hDPCs. The IGF-1 gene was expressed in a dose-dependent manner in TS-SCLF. These results indicate that TS-SC and TS-SCLF fermented extract effectively promoted hair growth and gene expression relevant to hair growth in hDPCs. Used in clinical trials the test substance 'CMK-LPF01' showed a statistically significant increase in the number of hairs at 8 weeks, 16 weeks, and 24 weeks compared to before product use, and a change in hair growth, a secondary efficacy evaluation variable. Through additional research in the future, it is expected that "CMK-LPF01" can be developed as a functional material that can help alleviate symptoms of hair loss.