Journal of Ginseng Research

  • 제47권3호
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  • Pages.440-447
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  • 2023
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  • 1226-8453(pISSN)
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  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
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Ginsenoside Re prevents 3-methyladenine-induced catagen phase acceleration by regulating Wnt/β-catenin signaling in human dermal papilla cells

  • 투고 : 2022.05.05
  • 심사 : 2022.11.03
  • 발행 : 2023.05.01
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초록

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.

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참고문헌

  1. Alonso L, Fuchs E. The hair cycle. J Cell Sci 2006;119:391-3. https://doi.org/10.1242/jcs.02793.
  2. Geyfman M, Plikus MV, Treffeisen E, Andersen B, Paus R. Resting no more: redefining telogen, the maintenance stage of the hair growth cycle. Biol Rev Camb Philos Soc 2015;90:1179-96. https://doi.org/10.1111/brv.12151.
  3. Schneider MR, Schmidt-Ullrich R, Paus R. The hair follicle as a dynamic miniorgan. Curr Biol 2009;19:R132-42. https://doi.org/10.1016/j.cub.2008.12.005.
  4. Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev 2001;81:449-94. https://doi.org/10.1152/physrev.2001.81.1.449.
  5. Paus R, Foitzik K. In search of the "hair cycle clock": a guided tour. Differentiation 2004;72:489-511. https://doi.org/10.1111/j.1432-0436.2004.07209004.x.
  6. Lee NE, Park SD, Hwang H, Choi SH, Lee RM, Nam SM, Choi JH, Rhim H, Cho IH, Kim HC, et al. Effects of a gintonin-enriched fraction on hair growth: an in vitro and in vivo study. J Ginseng Res 2020;44:168-77. https://doi.org/10.1016/j.jgr.2019.05.013.
  7. Keum DI, Pi LQ, Hwang ST, Lee WS. Protective effect of Korean Red Ginseng against chemotherapeutic drug-induced premature catagen development assessed with human hair follicle organ culture model. J Ginseng Res 2016;40:169-75. https://doi.org/10.1016/j.jgr.2015.07.004.
  8. Zhou L, Wang H, Jing J, Yu L, Wu X, Lu Z. Morroniside regulates hair growth and cycle transition via activation of the Wnt/β-catenin signaling pathway. Sci Rep 2018;8:13785. https://doi.org/10.1038/s41598-018-32138-2.
  9. Castela M, Linay F, Roy E, Moguelet P, Xu J, Holzenberger M, Khosrotehrani K, Aractingi S. Igf1r signalling acts on the anagen-to-catagen transition in the hair cycle. Exp Dermatol 2017;26:785-91. https://doi.org/10.1111/exd.13287.
  10. Bai X, Lei M, Shi J, Yu Y, Qiu W, Lai X, Liu Y, Yang T, Yang L, Widelitz RB, et al. Roles of gasderminA3 in catagen-telogen transition during hair cycling. J Invest Dermatol 2015;135:2162-72. https://doi.org/10.1038/jid.2015.147.
  11. Rishikaysh P, Dev K, Diaz D, Qureshi WM, Filip S, Mokry J. Signaling involved in hair follicle morphogenesis and development. Int J Mol Sci 2014;15:1647-70. https://doi.org/10.3390/ijms15011647.
  12. Enshell-Seijffers D, Lindon C, Kashiwagi M, Morgan BA. beta-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. Dev Cell 2010;18:633-42. https://doi.org/10.1016/j.devcel.2010.01.016.
  13. Gao C, Cao W, Bao L, Zuo W, Xie G, Cai T, Fu W, Zhang J, Wu W, Zhang X, et al. Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation. Nat Cell Biol 2010;12:781-90. https://doi.org/10.1038/ncb2082.
  14. Fan Q, Yang L, Zhang X, Ma Y, Li Y, Dong L, Zong Z, Hua X, Su D, Li H, et al. Autophagy promotes metastasis and glycolysis by upregulating MCT1 expression and Wnt/β-catenin signaling pathway activation in hepatocellular carcinoma cells. J Exp Clin Cancer Res 2018;37:9. https://doi.org/10.1186/s13046-018-0673-y.
  15. Jing Q, Li G, Chen X, Liu C, Lu S, Zheng H, Ma H, Qin Y, Zhang D, Zhang S, et al. Wnt3a promotes radioresistance via autophagy in squamous cell carcinoma of the head and neck. J Cell Mol Med 2019;23:4711-22. https://doi.org/10.1111/jcmm.14394.
  16. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol 2010;221:3-12. https://doi.org/10.1002/path.2697.
  17. Doherty J, Baehrecke EH. Life, death and autophagy. Nat Cell Biol 2018;20:1110-7. https://doi.org/10.1038/s41556-018-0201-5.
  18. Rubinsztein DC, Marino G, Kroemer G. Autophagy and aging. Cell 2011;146:682-95. https://doi.org/10.1016/j.cell.2011.07.030.
  19. Murrow L, Debnath J. Autophagy as a stress response and quality control mechanism: implications for cell injury and human disease. Annu Rev Pathol 2013;8:105-37. https://doi.org/10.1146/annurev-pathol-020712-163918.
  20. Kim JK, Shin KK, Kim H, Hong YH, Choi W, Kwak YS, Han CK, Hyun SH, Cho JY. Korean Red Ginseng exerts anti-inflammatory and autophagy-promoting activities in aged mice. J Ginseng Res 2021;45:717-25. https://doi.org/10.1016/j.jgr.2021.03.009.
  21. Choi W, Kim HS, Park SH, Kim D, Hong YD, Kim JH, Cho JY. Syringaresinol derived from Panax ginseng berry attenuates oxidative stress-induced skin aging via autophagy. J Ginseng Res 2022;46:536-42. https://doi.org/10.1016/j.jgr.2021.08.003.
  22. Hou J, Jeon B, Baek J, Yun Y, Kim D, Chang B, Kim S, Kim S. High fat dietinduced brain damaging effects through autophagy-mediated senescence, inflammation and apoptosis mitigated by ginsenoside F1-enhanced mixture. J Ginseng Res 2022;46:79-90. https://doi.org/10.1016/j.jgr.2021.04.002.
  23. Chai M, Jiang M, Vergnes L, Fu X, de Barros SC, Doan NB, Huang W, Chu J, Jiao J, Herschman H, et al. Stimulation of hair growth by small molecules that activate autophagy. Cell Rep 2019;27:3413-21. https://doi.org/10.1016/j.celrep.2019.05.070. e3.
  24. Parodi C, Hardman JA, Allavena G, Marotta R, Catelani T, Bertolini M, Paus R, Grimaldi B. Autophagy is essential for maintaining the growth of a human (mini-)organ: evidence from scalp hair follicle organ culture. PLOS Biol 2018;16:e2002864. https://doi.org/10.1371/journal.pbio.2002864.
  25. Yoshii SR, Mizushima N. Monitoring and measuring autophagy. Int J Mol Sci 2017;18:1865. https://doi.org/10.3390/ijms18091865.
  26. Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y. Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H4-II-E cells. Cell Struct Funct 1998;23:33-42. https://doi.org/10.1247/csf.23.33.
  27. Greco V, Chen T, Rendl M, Schober M, Amalia Pasolli H, Stokes N, Dela CruzRacelis J, Fuchs E. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell 2009;4:155-69. https://doi.org/10.1016/j.stem.2008.12.009.
  28. Koh E, Jang OH, Hwang KH, An YN, Moon BK. Effects of steaming and airdrying on ginsenoside composition of Korean ginseng (Panax ginseng C.A. Meyer). J Food Process Preserv 2015;39:207-13. https://doi.org/10.1111/jfpp.12412.
  29. Joo KM, Lee JH, Jeon HY, Park CW, Hong DK, Jeong HY, Lee SJ, Lee SY, Lim KM. Pharmacokinetic study of ginsenoside Re with pure ginsenoside Re and ginseng berry extracts in mouse using ultra performance liquid chromatography/mass spectrometric method. J Pharm Biomed Anal 2010;51:278-83. https://doi.org/10.1016/j.jpba.2009.08.013.
  30. Kim AD, Kang KA, Kim HS, Kim DH, Choi YH, Lee SJ, Kim HS, Hyun JW. A ginseng metabolite, compound K, induces autophagy and apoptosis via generation of reactive oxygen species and activation of JNK in human colon cancer cells. Cell Death Dis 2013;4:e750. https://doi.org/10.1038/cddis.2013.273.
  31. Mai TT, Moon JY, Song YW, Viet PQ, Phuc PV, Lee JM, Yi TH, Cho M, Cho SK. Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells. Cancer Lett 2012;321:144-53. https://doi.org/10.1016/j.canlet.2012.01.045.
  32. Zhuang J, Yin J, Xu C, Mu Y, Lv S. 20(S)-Ginsenoside Rh2 induce the apoptosis and autophagy in U937 and K562 cells. Nutrients 2018;10:328. https://doi.org/10.3390/nu10030328.
  33. Andl T, Reddy ST, Gaddapara T, Millar SE. WNT signals are required for the initiation of hair follicle development. Dev Cell 2002;2:643-53. https://doi.org/10.1016/s1534-5807(02)00167-3.
  34. Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 2002;22:1172-83. https://doi.org/10.1128/MCB.22.4.1172-1183.2002.
  35. Liu J, Xiao Q, Xiao J, Niu C, Li Y, Zhang X, Zhou Z, Shu G, Yin G. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther 2022;7:3. https://doi.org/10.1038/s41392-021-00762-6.
  36. Steinhart Z, Angers S. Wnt signaling in development and tissue homeostasis. Development 2018;145:dev146589. https://doi.org/10.1242/dev.146589.
  37. MacDonald BT, Tamai K, He X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell 2009;17:9-26. https://doi.org/10.1016/j.devcel.2009.06.016.
  38. Chien AJ, Conrad WH, Moon RT. A Wnt survival guide: from flies to human disease. J Invest Dermatol 2009;129:1614-27. https://doi.org/10.1038/jid.2008.445.
  39. Truong VL, Keum YS, Jeong WS. Red ginseng oil promotes hair growth and protects skin against UVC radiation. J Ginseng Res 2021;45:498-509. https://doi.org/10.1016/j.jgr.2020.12.008.
  40. Lee JH. Wnt signaling in hair follicle development. Asian J Beauty Cosmetol 2017;15:242-6. https://doi.org/10.20402/ajbc.2016.0141.
  41. Kishimoto J, Burgeson RE, Morgan BA. Wnt signaling maintains the hairinducing activity of the dermal papilla. Genes Dev 2000;14:1181-5. https://doi.org/10.1101/gad.14.10.1181
  42. Premanand A, Rajkumari BR. Androgen modulation of Wnt/β-catenin signaling in androgenetic alopecia. Arch Dermatol Res 2018;310:391-9. https://doi.org/10.1007/s00403-018-1826-8.
  43. Kim SN, Kim S, Hong YD, Park H, Shin SH, Kim AR, Park BC, Shin SS, Park JS, Park M, et al. The ginsenosides of Panax ginseng promote hair growth via similar mechanism of minoxidil. J Dermatol Sci 2015;77:132-4. https://doi.org/10.1016/j.jdermsci.2014.12.007.
  44. Lee Y, Kim SN, Hong YD, Park BC, Na Y. Panax ginseng extract antagonizes the effect of DKK-1-induced catagen-like changes of hair follicles. Int J Mol Med 2017;40:1194-200. https://doi.org/10.3892/ijmm.2017.3107.
  45. Higgins CA, Richardson GD, Ferdinando D, Westgate GE, Jahoda CAB. Modelling the hair follicle dermal papilla using spheroid cell cultures. Exp Dermatol 2010;19:546-8. https://doi.org/10.1111/j.1600-0625.2009.01007.x.
  46. Higgins CA, Chen JC, Cerise JE, Jahoda CAB, Christiano AM. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth. Proc Natl Acad Sci U S A 2013;110:19679. https://doi.org/10.1073/pnas.1309970110. -88.
  47. Oh JW, Kloepper J, Langan EA, Kim Y, Yeo J, Kim MJ, Hsi TC, Rose C, Yoon GS, Lee SJ, et al. A guide to studying human hair follicle cycling in vivo. J Invest Dermatol 2016;136:34-44. https://doi.org/10.1038/JID.2015.354.
  48. Kloepper JE, Sugawara K, Al-Nuaimi Y, Gasp ar E, van Beek N, Paus R. Methods in hair research: how to objectively distinguish between anagen and catagen in human hair follicle organ culture. Exp Dermatol 2010;19:305-12. https://doi.org/10.1111/j.1600-0625.2009.00939.x.