DOI QR코드

DOI QR Code

Udenafil Induces the Hair Growth Effect of Adipose-Derived Stem Cells

  • 투고 : 2018.10.08
  • 심사 : 2019.02.25
  • 발행 : 2019.07.01

초록

Udenafil, which is a $PDE_5$ inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafiltreated ASCs accelerated telogen-to-anagen transition in vivo. We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and $NF{\kappa}B$. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or $NF{\kappa}B$ knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and $NF{\kappa}B$ pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.

키워드

참고문헌

  1. Ackermann, L. W. and Denning, G. M. (2004) Nuclear factor-kappaB contributes to interleukin-4- and interferon-dependent polymeric immunoglobulin receptor expression in human intestinal epithelial cells. Immunology 111, 75-85. https://doi.org/10.1111/j.1365-2567.2004.01773.x
  2. Bao, K. and Reinhardt, R. L. (2015) The differential expression of IL-4 and IL-13 and its impact on type-2 immunity. Cytokine 75, 25-37. https://doi.org/10.1016/j.cyto.2015.05.008
  3. Buhl, A. E., Waldon, D. J., Kawabe, T. T. and Holland, J. M. (1989) Minoxidil stimulates mouse vibrissae follicles in organ culture. J. Dermatol. Sci. 92, 315-320.
  4. Bunnell, B. A., Estes, B. T., Guilak, F. and Gimble, J. M. (2008) Differentiation of adipose stem cells. Methods Mol. Biol. 456, 155-171. https://doi.org/10.1007/978-1-59745-245-8_12
  5. Celik, S. D. and Ates, O. (2018) Genetic analysis of interleukin 18 gene polymorphisms in alopecia areata. J. Clin. Lab. Anal. 32, e22386. https://doi.org/10.1002/jcla.22386
  6. Choi, N., Shin, S., Song, S. U. and Sung, J. H. (2018) Minoxidil promotes hair growth through stimulation of growth factor release from adipose-derived stem cells. Int. J. Mol. Sci. 19, E691. https://doi.org/10.3390/ijms19030691
  7. Dhayade, S., Kaesler, S, Sinnberg, T., Dobrowinski, H., Peters, S., Naumann, U., Liu, H., Hunger, R. E., Thunemann, M., Biedermann, T., Schittek, B., Simon, H. U., Feil, S. and Feil, R. (2016) Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth. Cell Rep. 14, 2599-2610. https://doi.org/10.1016/j.celrep.2016.02.028
  8. Festa, E., Fretz, J., Berry, R., Schmidt, B., Rodeheffer, M., Horowitz, M. and Horsley, V. (2011) Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling. Cell 146, 761-771. https://doi.org/10.1016/j.cell.2011.07.019
  9. Gopal, V. K., Francis. S. H. and Corbin, J. D. (2001) Allosteric sites of phosphodiesterase-5 (PDE5). A potential role in negative feedback regulation of cGMP signaling in corpus cavernosum. Eur. J. Biochem. 268, 3304-3312. https://doi.org/10.1046/j.1432-1327.2001.02233.x
  10. Gregoriou, S., Papafragkaki, D., Kontochristopoulos, G., Rallis, E., Kalogeromitros, D. and Rigopoulos, D. (2010) Cytokines and other mediators in alopecia areata. Mediators Inflamm. 2010, 928030. https://doi.org/10.1155/2010/928030
  11. Groves, R. W., Williams, I. R., Sarkar, S., Nakamura, K. and Kupper, T. S. (1994) Analysis of epidermal IL-1 family members in vivo using transgenic mouse models. J. Investig. Dermatol. 102, 556.
  12. Han, J. H., Kwon, O. S., Chung, J. H., Cho, K. H., Eun, H. C. and Kim, K. H. (2004) Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle. J. Dermatol. Sci. 34, 91-98. https://doi.org/10.1016/j.jdermsci.2004.01.002
  13. Headington, J. T. (1987) Hair follicle biology and topical minoxidil: possible mechanisms of action. Dermatologica 175, 19-22. https://doi.org/10.1159/000248894
  14. Hoffmann, R. T. (1999) The potential role of cytokines and T cells in alopecia areata. J. Investig. Dermatol. Symp. Proc. 4, 235-238. https://doi.org/10.1038/sj.jidsp.5640218
  15. Hoffmann, R. and Happle, R. (1995) Does interleukin-1 induce hair loss? Dermatology 191, 273-275. https://doi.org/10.1159/000246567
  16. Hoke, N. N., Salloum, F. N., Kass, D. A., Das, A. and Kukreja, R. C. (2012) Preconditioning by phosphodiesterase-5 inhibition improves therapeutic efficacy of adipose-derived stem cells following myocardial infarction in mice. Stem Cells 30, 326-335. https://doi.org/10.1002/stem.789
  17. Jeong, H. H., Piao, S., Ha, J. N., Kim, I. G., Oh, S. H., Lee, J. H., Cho, H. J., Hong, S. H., Kim, S. W. and Lee, J. Y. (2013a) Combined therapeutic effect of udenafil and adipose-derived stem cell (ADSC)/brain-derived neurotrophic factor (BDNF)-membrane system in a rat model of cavernous nerve injury. Urology 81, 1108.e7-1108.e14. https://doi.org/10.1016/j.urology.2013.01.022
  18. Jeong, Y. M., Sung, Y. K., Kim, W. K., Kim, J. H., Kwack, M. H., Yoon, I., Kim, D. D. and Sung, J. H. (2013b) Ultraviolet B preconditioning enhances the hair growth-promoting effects of adipose-derived stem cells via generation of reactive oxygen species. Stem Cells Dev. 22, 158-168. https://doi.org/10.1089/scd.2012.0167
  19. Jin, S. E. and Sung, J. H. (2016) Hair regeneration using adiposederived stem cells. Histol. Histopathol. 31, 249-256.
  20. Kang, K. K., Choi, S. M., Ahn, G. J., Kwon, J. W. and Kim, W. B. (2004) The effect of DA-8159 oncorpus cavernosal smooth muscle relaxation and penile erection in diabetic rabbits. Urol. Res. 32, 107-111. https://doi.org/10.1007/s00240-003-0387-1
  21. Kim, J. H., Kim, W. K., Sung, Y. K., Kwack, M. H., Song, S. Y., Choi, J. S., Park, S. G., Yi, T., Lee, H. J., Kim, D. D., Seo, H. M., Song, S. U. and Sung, J. H. (2014a) The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adiposederived stem cells. Stem Cells Dev. 23, 1364-1376. https://doi.org/10.1089/scd.2013.0460
  22. 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
  23. Kim, J. H., Park, S. H., Park, S. G., Choi, J. S., Xia, Y. and Sung, J. H. (2011) The pivotal role of reactive oxygen species generation in the hypoxia-induced stimulation of adipose-derived stem cells. Stem Cells Dev. 20, 1753-1761. https://doi.org/10.1089/scd.2010.0469
  24. Kim, W. S., Han, L., Hwang, S. J., Sung, J. H. (2014b) An update on niche composition, signaling and functional regulation of adiposederived stem cell. Expert Opin. Biol. Ther. 14, 1091-1102. https://doi.org/10.1517/14712598.2014.907785
  25. Kim, W. S., Park, B. S., Sung, J. H., Yang, J. M., Park, S. B., Kwak, S. J. and Park, J. S. (2007) Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. J. Dermatol. Sci. 48, 15-24. https://doi.org/10.1016/j.jdermsci.2007.05.018
  26. Kwack, M. H., Kang, B. M., Kim, M. K., Kim, J. C. and Sung, Y. K. (2011) Minoxidil activates beta-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect. J. Dermatol. Sci. 62, 154-159. https://doi.org/10.1016/j.jdermsci.2011.01.013
  27. Lee, C. H., Kim, H. S., Goo, M. J., Kang, K. K., Ahn, B. O., Kim, S. H. and Yang D. Y. (2011) Chronic administration of udenafil, a selective phosphodiesterase type 5 inhibitor, promotes erectile function recovery in an animal model of bilateral cavernous nerve crush injury. J. Sex Med. 8, 1330-1340. https://doi.org/10.1111/j.1743-6109.2011.02228.x
  28. Li, M., Marubayashi, A., Nakaya, Y., Fukui, K. and Arase, S. (2001) Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil. J. Invest. Dermatol. 117, 1594-1600. https://doi.org/10.1046/j.0022-202x.2001.01570.x
  29. Mandt, N., Geilen, C. C., Wrobel, A., Gelber, A., Kamp, H., Orfanos, C. E. and Blume-Peytavi, U. (2002) Interleukin-4 induces apoptosis in cultured human follicular keratinocytes, but not in dermal papilla cells. Eur. J. Dermatol. 12, 432-438.
  30. Michelet, J. F., Commo, S., Billoni, N., Mahe, Y. F. and Bernard, B. A. (1997) Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect. J. Invest. Dermatol. 108, 205-209. https://doi.org/10.1111/1523-1747.ep12334249
  31. Otomo, S. (2002) Hair growth effect of minoxidil. Nihon Yakurigaku Zasshi 119, 167-74. https://doi.org/10.1254/fpj.119.167
  32. Paick, J. S., Kim, S. W., Park, Y. K., Hyun, J. S., Park, N. C., Lee, S. W., Park, K., Moon, K. H. and Chung, W. S. (2009) The efficacy and safety of udenafil [Zydena] for the treatment of erectile dysfunction in hypertensive men taking concomitant antihypertensive agents. J. Sex Med. 6, 3166-3176. https://doi.org/10.1111/j.1743-6109.2009.01456.x
  33. Perez-Meza, D., Ziering, C., Sforza, M., Krishnan, G., Ball, E. and Daniels, E. (2017) Hair follicle growth by stromal vascular fractionenhanced adipose transplantation in baldness. Stem Cells Cloning 10, 1-10. https://doi.org/10.2147/SCCAA.S131431
  34. Pyriochou, A., Zhou, Z., Koika, V., Petrou, C., Cordopatis, P., Sessa, W. C. and Papapetropoulos, A. (2007) The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway. J. Cell. Physiol. 211, 197-204. https://doi.org/10.1002/jcp.20929
  35. Ramot, Y., Marzani, B., Pinto, D., Sorbellini, E. and Rinaldi, F. (2018) IL-17 inhibition: is it the long-awaited savior for alopecia areata? Arch. Dermatol. Res. 310, 383-390. https://doi.org/10.1007/s00403-018-1823-y
  36. Redler, S., Albert, F., Brockschmidt, F. F., Herold, C., Hanneken, S., Eigelshoven, S., Giehl, K. A., Kruse, R., Lutz, G., Wolff, H., Blaumeiser, B., Bohm, M., Becker, T., Nothen, M. M. and Betz, R. C. (2012) Investigation of selected cytokine genes suggests that IL- 2RA and the TNF/LTA locus are risk factors for severe alopecia areata. Br. J. Dermatol. 167, 1360-1365. https://doi.org/10.1111/bjd.12004
  37. Sahara, M., Sata, M., Morita, T., Nakajima. T., Hirata, Y. and Nagai, R. (2010) A phosphodiesterase-5 inhibitor vardenafil enhances angiogenesis through a protein kinase G-dependent hypoxia-inducible factor-1/vascular endothelial growth factor pathway. Arterioscler. Thromb. Vasc. Biol. 30, 1315-1324. https://doi.org/10.1161/ATVBAHA.109.201327
  38. Won, C. H., Yoo, H. G., Kwon, O. S., Sung, M. Y, Kang, Y. J., Chung, J. H., Park, B. S., Sung, J. H., Kim, W. S. and Kim, K. H. (2010) Hair growth promoting effects of adipose tissue-derived stem cells. J. Dermatol. Sci. 57, 134-137. https://doi.org/10.1016/j.jdermsci.2009.10.013
  39. Yang, Y., Choi, H., Seon, M., Cho, D. and Bang, S. I. (2016) LL-37 stimulates the functions of adipose-derived stromal/stem cells via early growth response 1 and the MAPK pathway. Stem Cell Res. Ther. 7, 58. https://doi.org/10.1186/s13287-016-0313-4
  40. Yi, T., Kim, W. K., Choi, J. S., Song, S. Y., Han, J., Kim, J. H., Kim, W. S., Park, S. G., Lee, H. J., Cho, Y. K., Hwang, S. J., Song, S. U. and Sung, J. H. (2014) Isolation of adipose-derived stem cells by using a subfractionation culturing method. Expert Opin. Biol. Ther. 14, 1551-1560. https://doi.org/10.1517/14712598.2014.943661

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