DOI QR코드

DOI QR Code

Hair Growth Promotion by δ-Opioid Receptor Activation

  • Received : 2021.04.01
  • Accepted : 2021.05.26
  • Published : 2021.11.01

Abstract

Literature has revealed that the delta opioid receptor (DOR) exhibited diverse pharmacological effects on neuron and skin. In the present study, we have investigated whether the activation of DOR has hair-growth promotion effects. Compared with other opioid receptor, DOR was highly expressed in epidermal component of hair follicle in human and rodents. The expression of DOR was high in the anagen phase, but it was low in the catagen and telogen phases during mouse hair cycle. Topical application of UFP-512, a specific DOR agonist, significantly accelerated the induction of the anagen in C3H mice. Topical application of UFP-512 also increased the hair length in hair organ cultures and promoted the proliferation and the migration of outer root sheath (ORS) cells. Similarly, pharmacological inhibition of DOR by naltrindole significantly inhibited the anagen transition process and decreased hair length in hair organ cultures. Thus, we further examined whether Wnt/β-catenin pathway was related to the effects of DOR on hair growth. We found that Wnt/β-catenin pathway was activated by UFP-512 and siRNA for β-catenin attenuated the UFP-512 induced proliferation and migration of ORS cells. Collectively, result established that DOR was involved in hair cycle regulation, and that DOR agonists such as UFP-512 should be developed for novel hair-loss treatment.

Keywords

Acknowledgement

Korean Government and the Tech Incubator Program for Starup Korea (Grant No. 10388970).

References

  1. Aberle, H., Bauer, A., Stappert, J., Kispert, A. and Kemler, R. (1997) Beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J. 16, 3797-3804. https://doi.org/10.1093/emboj/16.13.3797
  2. Aguila, B., Coulbault, L., Boulouard, M., Leveille, F., Davis, A., Toth, G., Borsodi, A., Balboni, G., Salvadori, S., Jauzac, P. and Allouche, S. (2007) In vitro and in vivo pharmacological profile of UFP-512, a novel selective delta-opioid receptor agonist; correlations between desensitization and tolerance. Br. J. Pharmacol. 152, 1312-1324. https://doi.org/10.1038/sj.bjp.0707497
  3. Andl, T., Reddy, S. T., Gaddapara, T. and Millar, S. E. (2002) WNT signals are required for the initiation of hair follicle development. Dev. Cell 2, 643-653. https://doi.org/10.1016/S1534-5807(02)00167-3
  4. Bigliardi-Qi, M., Bigliardi, P. L., Eberle, A. N., Buchner, S. and Rufli, T. (2000) Beta-endorphin stimulates cytokeratin 16 expression and downregulates mu-opiate receptor expression in human epidermis. J. Invest. Dermatol. 114, 527-532. https://doi.org/10.1046/j.1523-1747.2000.00801.x
  5. Bigliardi-Qi, M., Gaveriaux-Ruff, C., Zhou, H., Hell, C., Bady, P., Rufli, T., Kieffer, B. and Bigliardi, P. (2006) Deletion of delta-opioid receptor in mice alters skin differentiation and delays wound healing. Differentiation 74, 174-185. https://doi.org/10.1111/j.1432-0436.2006.00065.x
  6. Bigliardi, P. L., Dancik, Y., Neumann, C. and Bigliardi-Qi, M. (2016) Opioids and skin homeostasis, regeneration and ageing - what's the evidence? Exp. Dermatol. 25, 586-591. https://doi.org/10.1111/exd.13021
  7. Bigliardi, P. L., Neumann, C., Teo, Y. L., Pant, A. and Bigliardi-Qi, M. (2015) Activation of the delta-opioid receptor promotes cutaneous wound healing by affecting keratinocyte intercellular adhesion and migration. Br. J. Pharmacol. 172, 501-514. https://doi.org/10.1111/bph.12687
  8. Cao, S., Chao, D., Zhou, H., Balboni, G. and Xia, Y. (2015) A novel mechanism for cytoprotection against hypoxic injury: delta-opioid receptor-mediated increase in Nrf2 translocation. Br. J. Pharmacol. 172, 1869-1881. https://doi.org/10.1111/bph.13031
  9. Charbaji, N., Schafer-Korting, M. and Kuchler, S. (2012) Morphine stimulates cell migration of oral epithelial cells by delta-opioid receptor activation. PLoS ONE 7, e42616. https://doi.org/10.1371/journal.pone.0042616
  10. Chen, D., Jarrell, A., Guo, C., Lang, R. and Atit, R. (2012) Dermal betacatenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation. Development 139, 1522-1533. https://doi.org/10.1242/dev.076463
  11. Collins, C. A., Kretzschmar, K. and Watt, F. M. (2011) Reprogramming adult dermis to a neonatal state through epidermal activation of beta-catenin. Development 138, 5189-5199. https://doi.org/10.1242/dev.064592
  12. Fu, J. and Hsu, W. (2013) Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis. J. Invest. Dermatol. 133, 890-898. https://doi.org/10.1038/jid.2012.407
  13. Furkert, J., Klug, U., Slominski, A., Eichmuller, S., Mehlis, B., Kertscher, U. and Paus, R. (1997) Identification and measurement of beta-endorphin levels in the skin during induced hair growth in mice. Biochim. Biophys. Acta 1336, 315-322. https://doi.org/10.1016/S0304-4165(97)00046-9
  14. He, X., Sandhu, H. K., Yang, Y., Hua, F., Belser, N., Kim, D. H. and Xia, Y. (2013) Neuroprotection against hypoxia/ischemia: delta-opioid receptor-mediated cellular/molecular events. Cell. Mol. Life Sci. 70, 2291-2303. https://doi.org/10.1007/s00018-012-1167-2
  15. Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G. and Birchmeier, W. (2001) Beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105, 533-545. https://doi.org/10.1016/S0092-8674(01)00336-1
  16. Ito, M., Yang, Z., Andl, T., Cui, C., Kim, N., Millar, S. E. and Cotsarelis, G. (2007) Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447, 316-320. https://doi.org/10.1038/nature05766
  17. Jindo, T., Tsuboi, R., Imai, R., Takamori, K., Rubin, J. S. and Ogawa, H. (1994) Hepatocyte growth factor/scatter factor stimulates hair growth of mouse vibrissae in organ culture. J. Invest. Dermatol. 103, 306-309. https://doi.org/10.1111/1523-1747.ep12394731
  18. Li, Y., Wang, J., Li, Z., Cheng, H., Zhang, Z., Luo, T., Zhang, X., Gao, G., Lu, H. and Li, L. (2019) Propoxyphene mediates oxyhemoglobin-induced injury in rat cortical neurons through up-regulation of active-beta-catenin. Front. Pharmacol. 10, 1616. https://doi.org/10.3389/fphar.2019.01616
  19. Kim, J. H., Park, S. G., Kim, W. K., Song, S. U. and Sung, J. H. (2015) Functional regulation of adipose-derived stem cells by PDGFD. Stem Cells 33, 542-556. https://doi.org/10.1002/stem.1865
  20. Mabrouk, O. S., Marti, M., Salvadori, S. and Morari, M. (2009) The novel delta opioid receptor agonist UFP-512 dually modulates motor activity in hemiparkinsonian rats via control of the nigro-thalamic pathway. Neuroscience 164, 360-369. https://doi.org/10.1016/j.neuroscience.2009.08.058
  21. Marie, N., Lecoq, I., Jauzac, P. and Allouche, S. (2003) Differential sorting of human delta-opioid receptors after internalization by peptide and alkaloid agonists. J. Biol. Chem. 278, 22795-22804. https://doi.org/10.1074/jbc.M300084200
  22. McLaughlin, P. J., Pothering, C. A., Immonen, J. A. and Zagon, I. S. (2011) Topical treatment with the opioid antagonist naltrexone facilitates closure of full-thickness wounds in diabetic rats. Exp. Biol. Med. (Maywood) 236, 1122-1132. https://doi.org/10.1258/ebm.2011.011163
  23. Neumann, C., Bigliardi-Qi, M., Widmann, C. and Bigliardi, P. L. (2015) The delta-opioid receptor affects epidermal homeostasis via ERK-dependent inhibition of transcription factor POU2F3. J. Invest. Dermatol. 135, 471-480. https://doi.org/10.1038/jid.2014.370
  24. Polastron, J., Mur, M., Mazarguil, H., Puget, A., Meunier, J. C. and Jauzac, P. (1994) SK-N-BE: a human neuroblastoma cell line containing two subtypes of delta-opioid receptors. J. Neurochem. 62, 898-906. https://doi.org/10.1046/j.1471-4159.1994.62030898.x
  25. Poonawala, T., Levay-Young, B. K., Hebbel, R. P. and Gupta, K. (2005) Opioids heal ischemic wounds in the rat. Wound Repair Regen. 13, 165-174. https://doi.org/10.1111/j.1067-1927.2005.130207.x
  26. Qiu, J., Chao, D., Sheng, S., Khiati, D., Zhou, X. and Xia, Y. (2019) Delta-opioid receptor-Nrf-2-mediated inhibition of inflammatory cytokines in neonatal hypoxic-ischemic encephalopathy. Mol. Neurobiol. 56, 5229-5240. https://doi.org/10.1007/s12035-018-1452-7
  27. Reyes, B. A., Vakharia, K., Ferraro, T. N., Levenson, R., Berrettini, W. H. and Van Bockstaele, E. J. (2012) Opiate agonist-induced redistribution of Wntless, a mu-opioid receptor interacting protein, in rat striatal neurons. Exp. Neurol. 233, 205-213. https://doi.org/10.1016/j.expneurol.2011.09.037
  28. Sheng, S., Huang, J., Ren, Y., Zhi, F., Tian, X., Wen, G., Ding, G., Xia, T. C., Hua, F. and Xia, Y. (2018) Neuroprotection against hypoxic/ischemic injury: delta-opioid receptors and BDNF-TrkB pathway. Cell. Physiol. Biochem. 47, 302-315. https://doi.org/10.1159/000489808
  29. Tortelly, V. D., De Mattos, T., Fernandes, L. S. A., Nunes, B. E. M. and Melo, D. F. (2019) Low-dose naltrexone: a novel adjunctive treatment in symptomatic alopecias? Dermatol. Online J. 25, 13030/qt6j45h81f.
  30. Vergura, R., Balboni, G., Spagnolo, B., Gavioli, E., Lambert, D. G., McDonald, J., Trapella, C., Lazarus, L. H., Regoli, D., Guerrini, R., Salvadori, S. and Calo, G. (2008) Anxiolytic- and antidepressant-like activities of H-Dmt-Tic-NH-CH(CH2-COOH)-Bid (UFP-512), a novel selective delta opioid receptor agonist. Peptides 29, 93-103. https://doi.org/10.1016/j.peptides.2007.10.012
  31. Wang, J., Zhu, G., Huang, L., Nie, T., Tao, K., Li, Y. and Gao, G. (2017) Morphine administration induces change in anxiety-related behavior via Wnt/beta-catenin signaling. Neurosci. Lett. 639, 199-206. https://doi.org/10.1016/j.neulet.2017.01.005
  32. Yang, Y., Zhi, F., He, X., Moore, M. L., Kang, X., Chao, D., Wang, R., Kim, D. H. and Xia, Y. (2012) Delta-opioid receptor activation and microRNA expression of the rat cortex in hypoxia. PLoS ONE 7, e51524. https://doi.org/10.1371/journal.pone.0051524
  33. Zaki, P. A., Bilsky, E. J., Vanderah, T. W., Lai, J., Evans, C. J. and Porreca, F. (1996) Opioid receptor types and subtypes: the delta receptor as a model. Annu. Rev. Pharmacol. Toxicol. 36, 379-401. https://doi.org/10.1146/annurev.pa.36.040196.002115