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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Wnt/β-catenin signaling activator restores hair regeneration suppressed by diabetes mellitus

  • Yeong Chan, Ryu (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • You-rin, Kim (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Jiyeon, Park (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Sehee, Choi (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Geon-Uk, Kim (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Eunhwan, Kim (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Yumi, Hwang (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Heejene, Kim (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Soon Sun, Bak (Department of Immunology, School of Medicine, Kyungpook National University) ;
  • Jin Eun, Lee (Department of Immunology, School of Medicine, Kyungpook National University) ;
  • Young Kwan, Sung (Department of Immunology, School of Medicine, Kyungpook National University) ;
  • Gyoonhee, Han (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Soung-Hoon, Lee (CK Regeon Inc., Engineering Research Park) ;
  • Kang-Yell, Choi (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University)
  • Received : 2022.05.06
  • Accepted : 2022.08.02
  • Published : 2022.11.30
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Abstract

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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (2019R1A2C3002751, 2020M3E5E2040018). Y.C RYU was supported by a Brain Korea 21 (BK21) FOUR studentship from the NRF.

References

  1. Klonoff DC (2009) The increasing incidence of diabetes in the 21st century. J Diabetes Sci Technol 3, 1-2  https://doi.org/10.1177/193229680900300101
  2. Blair M (2016) Diabetes mellitus review. Urol Nurs 36, 27-36  https://doi.org/10.7257/1053-816x.2016.36.1.27
  3. Yeo HJ, Shin MJ, Kim DW, Kwon HY, Eum WS and Choi SY (2021) Tat-CIAPIN1 protein prevents against cytokineinduced cytotoxicity in pancreatic RINm5F β-cells. BMB Rep 54, 458-463 https://doi.org/10.5483/BMBRep.2021.54.9.040
  4. Munana KR (1995) Long-term complications of diabetes mellitus, Part I: Retinopathy, nephropathy, neuropathy. Vet Clin North Am Small Anim Pract 25, 715-730 
  5. Chen Q and Ma JX (2017) Canonical Wnt signaling in diabetic retinopathy. Vision Res 139, 47-58  https://doi.org/10.1016/j.visres.2017.02.007
  6. Qi W, Yang C, Dai Z et al (2015) High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling. Diabetes 64, 1407-1419  https://doi.org/10.2337/db14-1111
  7. Kim DY, Jung SY, Kim K and Kim CJ (2016) Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats. J Exerc Rehabil 12, 276-283  https://doi.org/10.12965/jer.1632678.339
  8. Wang M, Yao S, He D et al (2022) Type 2 diabetic mellitus inhibits skin renewal through inhibiting WNTdependent Lgr5+ hair follicle stem cell activation in C57BL/6 mice. J Diabetes Res 2022, 8938276 
  9. Jang WS, Son IP, Yeo IK et al (2013) The annual changes of clinical manifestation of androgenetic alopecia clinic in korean males and females: a outpatient-based study. Ann Dermatol 25, 181-188  https://doi.org/10.5021/ad.2013.25.2.181
  10. Lei M, Guo H, Qiu W et al (2014) Modulating hair follicle size with Wnt10b/DKK1 during hair regeneration. Exp Dermatol 23, 407-413  https://doi.org/10.1111/exd.12416
  11. Stamos JL and Weis WI (2013) The β-catenin destruction complex. Cold Spring Harb Perspect Biol 5, a007898 https://doi.org/10.1101/cshperspect.a007898
  12. MacDonald BT, Tamai K and He X (2009) Wnt/betacatenin signaling: components, mechanisms, and diseases. Dev Cell 17, 9-26  https://doi.org/10.1016/j.devcel.2009.06.016
  13. Enshell-Seijffers D, Lindon C, Kashiwagi M and Morgan BA (2010) beta-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. Dev Cell 18, 633-642  https://doi.org/10.1016/j.devcel.2010.01.016
  14. Ito M, Yang Z, Andl T et al (2007) Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447, 316-320  https://doi.org/10.1038/nature05766
  15. Yamauchi K and Kurosaka A (2009) Inhibition of glycogen synthase kinase-3 enhances the expression of alkaline phosphatase and insulin-like growth factor-1 in human primary dermal papilla cell culture and maintains mouse hair bulbs in organ culture. Arch Dermatol Res 301, 357-365  https://doi.org/10.1007/s00403-009-0929-7
  16. Mahmoud EA, Elgarhy LH, Hasby EA and Mohammad L (2019) Dickkopf-1 expression in androgenetic alopecia and alopecia areata in male patients. Am J Dermatopathol 41, 122-127  https://doi.org/10.1097/DAD.0000000000001266
  17. Tasaki N, Minematsu T, Mugita Y, Ikeda S, Nakagami G and Sanada H (2016) Telogen elongation in the hair cycle of ob/ob mice. Biosci Biotechnol Biochem 80, 74-79  https://doi.org/10.1080/09168451.2015.1069693
  18. Ryu YC, Lee DH, Shim J et al (2021) KY19382, a novel activator of Wnt/β-catenin signalling, promotes hair regrowth and hair follicle neogenesis. Br J Pharmacol 178, 2533-2546 https://doi.org/10.1111/bph.15438
  19. Muller-Rover S, Handjiski B, van der Veen C et al (2001) A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol 117, 3-15  https://doi.org/10.1046/j.0022-202x.2001.01377.x
  20. Lee SH, Seo SH, Lee DH, Pi LQ, Lee WS and Choi KY (2017) Targeting of CXXC5 by a competing peptide stimulates hair regrowth and wound-induced hair neogenesis. J Invest Dermatol 137, 2260-2269  https://doi.org/10.1016/j.jid.2017.04.038
  21. Lyle S, Christofidou-Solomidou M, Liu Y, Elder DE, Albelda S and Cotsarelis G (1998) The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. J Cell Sci 111 ( Pt 21), 3179-3188  https://doi.org/10.1242/jcs.111.21.3179
  22. Gay D, Kwon O, Zhang Z et al (2013) Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding. Nat Med 19, 916-923 https://doi.org/10.1038/nm.3181
  23. Fan C, Luedtke MA, Prouty SM, Burrows M, Kollias N and Cotsarelis G (2011) Characterization and quantification of wound-induced hair follicle neogenesis using in vivo confocal scanning laser microscopy. Skin Res Technol 17, 387-397  https://doi.org/10.1111/j.1600-0846.2011.00508.x
  24. Linas SL and Nies AS (1981) Minoxidil. Ann Intern Med 94, 61-65  https://doi.org/10.7326/0003-4819-94-1-61
  25. Ceriello A, dello Russo P, Amstad P and Cerutti P (1996) High glucose induces antioxidant enzymes in human endothelial cells in culture. Evidence linking hyperglycemia and oxidative stress. Diabetes 45, 471-477  https://doi.org/10.2337/diabetes.45.4.471
  26. Nie X, Zhang H, Shi X et al (2020) Asiaticoside nitric oxide gel accelerates diabetic cutaneous ulcers healing by activating Wnt/β-catenin signaling pathway. Int Immunopharmacol 79, 106109 https://doi.org/10.1016/j.intimp.2019.106109
  27. Garza LA, Yang CC, Zhao T et al (2011) Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. J Clin Invest 121, 613-622  https://doi.org/10.1172/JCI44478
  28. Li J, Jiang TX, Hughes MW et al (2012) Progressive alopecia reveals decreasing stem cell activation probability during aging of mice with epidermal deletion of DNA methyltransferase 1. J Invest Dermatol 132, 2681-2690  https://doi.org/10.1038/jid.2012.206
  29. Choi BY (2020) Targeting Wnt/β-catenin pathway for developing therapies for hair loss. Int J Mol Sci 21
  30. Lee SH, Yoon J, Shin SH et al (2012) Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells. PLoS One 7, e34152  https://doi.org/10.1371/journal.pone.0034152
  31. Lim CH, Sun Q, Ratti K et al (2018) Hedehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing. Nat Commun 9, 4903  https://doi.org/10.1038/s41467-018-07142-9
  32. Werth VP, White WL, Sanchez MR and Franks AG (1992) Incidence of alopecia areata in lupus erythematosus. Arch Dermatol 128, 368-371  https://doi.org/10.1001/archderm.1992.01680130082010
  33. Ye Y, Zhang X, Zhao Y et al (2014) The clinical and trichoscopic features of syphilitic alopecia. J Dermatol Case Rep 8, 78-80 
  34. Patel D, Li P, Bauer AJ and Castelo-Soccio L (2017) Screening guidelines for thyroid function in children with alopecia areata. JAMA Dermatol 153, 1307-1310  https://doi.org/10.1001/jamadermatol.2017.3694
  35. Gilhar A and Kalish RS (2006) Alopecia areata: a tissue specific autoimmune disease of the hair follicle. Autoimmun Rev 5, 64-69  https://doi.org/10.1016/j.autrev.2005.07.001
  36. Shi J, Chi S, Xue J, Yang J, Li F and Liu X (2016) Emerging role and therapeutic implication of Wnt signaling pathways in autoimmune diseases. J Immunol Res 2016, 9392132 
  37. Park HJ, Kim MK, Kim Y, Kim HJ, Bae SK and Bae MK (2021) Neuromedin B modulates phosphate-induced vascular calcification. BMB Rep 54, 569-574  https://doi.org/10.5483/BMBRep.2021.54.11.089
  38. Taniyama M, Kushima K, Ban Y et al (1991) Simultaneous development of insulin dependent diabetes mellitus and alopecia areata universalis. Am J Med Sci 301, 269-271 https://doi.org/10.1097/00000441-199104000-00009