Chemokina CXCL12 – udział w cyklu życiowym włosa oraz nowe możliwości terapii łysienia androgenowego oraz plackowatego

Wiktor Jakieła; Aleksandra Kiszka; Jakub Kancerek; Szymon Trybuś; Doinika Hamerla

Chemokina CXCL12 – udział w cyklu życiowym włosa oraz nowe możliwości terapii łysienia androgenowego oraz plackowatego

Authors

Wiktor Jakieła, ; Aleksandra Kiszka; Jakub Kancerek; Szymon Trybuś; Doinika Hamerla

Keywords:

łysienie androgenowe, Łysienie plackowate, CXCL12

Synopsis

C-X-C Motif Chemokine Ligand 12 (CXCL12) odgrywa kluczową rolę w regulacji cyklu włosowego oraz w patogenezie łysienia androgenowego (AGA) i plackowatego (AA). Badania wykazały, że ekspresja CXCL12 jest wysoka w fibroblastach skórnych oraz w brodawkach włosa, a jej poziom wzrasta w fazach katagenu i telogenu, co koreluje z zahamowaniem wzrostu włosów. W AGA androgeny indukują ekspresję CXCL12 w komórkach brodawki skórnej i osłonki dermalnej, co prowadzi do miniaturyzacji mieszków włosowych poprzez aktywację szlaku CXCR4/STAT3/STAT5. W AA CXCL12 może działać jako czynnik rekrutujący limfocyty T CD8+, nasilając reakcję autoimmunologiczną przeciwko mieszkowi włosowemu. Neutralizacja CXCL12 za pomocą przeciwciał monoklonalnych wykazała potencjał terapeutyczny, prowadząc do przyspieszenia przejścia telogen-anagen oraz zwiększenia długości włosa w ludzkich modelach hodowli mieszków włosowych i zwierzęcych. Niniejsza praca ma na celu pogłębioną analizę mechanizmów molekularnych leżących u podstaw roli CXCL12 w AGA i AA oraz ocenę możliwości jej modulacji jako strategii terapeutycznej w leczeniu łysienia.

References

G. Severi, R. Sinclair, J.L. Hopper, D.R. English, M.R.E. McCredie, P. Boyle, G.G. Giles, Androgenetic alopecia in men aged 40–69 years: prevalence and risk factors, British Journal of Dermatology, Volume 149, Issue 6, 1 December 2003, Pages 1207–1213, https://doi.org/10.1111/j.1365-2133.2003.05565.x

Oiwoh, Sebastine Oseghae1; Enitan, Ademola Olusegun2; Adegbosin, Olubola Titilope3; Akinboro, Adeolu Oladayo4; Onayemi, Emmanuel Olaniyi5. Androgenetic Alopecia: A Review. Nigerian Postgraduate Medical Journal 31(2): p 85-92, Apr–Jun 2024. | DOI: 10.4103/npmj.npmj_47_24

Gan, D. C. & Sinclair, R. D. (2005). Prevalence of Male and Female Pattern Hair Loss in Maryborough. The Journal of Investigative Dermatology Symposium Proceedings, 10 (3), 184-189.

Budd D, Himmelberger D, Rhodes T, Cash TE, Girman CJ. The effects of hair loss in European men: a survey in four countries. Eur J Dermatol. 2000 Mar;10(2):122-7. PMID: 10694311.

Thomas F Cash, The psychology of hair loss and its implications for patient care, Clinics in Dermatology, Volume 19, Issue 2, 2001, Pages 161-166, ISSN 0738-081X, https://doi.org/10.1016/S0738-081X(00)00127-9.

Otberg N, Finner AM, Shapiro J. Androgenetic alopecia. Endocrinol Metab Clin North Am. 2007 Jun;36(2):379-98. doi: 10.1016/j.ecl.2007.03.004. PMID: 17543725.

Takashima, I., Iju, M., Sudo, M. (1981). Alopecia Androgenetica — Its Incidence in Japanese and Associated Conditions. In: Orfanos, C.E., Montagna, W., Stüttgen, G. (eds) Hair Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81650-5_42

J‐H. Paik, J‐B. Yoon, W‐Y. Sim, B‐S. Kim, N‐I. Kim, The prevalence and types of androgenetic alopecia in Korean men and women, British Journal of Dermatology, Volume 145, Issue 1, 1 July 2001, Pages 95–99, https://doi.org/10.1046/j.1365-2133.2001.04289.x

Hamilton, J.B. (1951), PATTERNED LOSS OF HAIR IN MAN: TYPES AND INCIDENCE. Annals of the New York Academy of Sciences, 53: 708-728. https://doi.org/10.1111/j.1749-6632.1951.tb31971.x

Alessandrini, A., Bruni, F., Piraccini, B.M. and Starace, M. (2021), Common causes of hair loss – clinical manifestations, trichoscopy and therapy. J Eur Acad Dermatol Venereol, 35: 629-640. https://doi.org/10.1111/jdv.17079

Kayvon H. Safavi, Sigfrid A. Muller, Vera J. Suman, Alan N. Moshell, L. Joseph Melton, Incidence of Alopecia Areata in Olmsted County, Minnesota, 1975 Through 1989, Mayo Clinic Proceedings, Volume 70, Issue 7, 1995, Pages 628-633, ISSN 0025-6196, https://doi.org/10.4065/70.7.628.

Pratt CH, King LE Jr, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers. 2017 Mar 16;3:17011. doi: 10.1038/nrdp.2017.11. PMID: 28300084; PMCID: PMC5573125.

Mirzoyev SA, Schrum AG, Davis MDP, Torgerson RR. Lifetime incidence risk of alopecia areata estimated at 2.1% by Rochester Epidemiology Project, 1990-2009. J Invest Dermatol. 2014 Apr;134(4):1141-1142. doi: 10.1038/jid.2013.464. Epub 2013 Nov 11. PMID: 24202232; PMCID: PMC3961558.

Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol. 2015 Jul 24;8:397-403. doi: 10.2147/CCID.S53985. PMID: 26244028; PMCID: PMC4521674.

Muth, J.L. and Cash, T.F. (1997), Body-Image Attitudes: What Difference Does Gender Make?1. Journal of Applied Social Psychology, 27: 1438-1452. https://doi.org/10.1111/j.1559-1816.1997.tb01607.x

Park AM, Khan S, Rawnsley J. Hair Biology: Growth and Pigmentation. Facial Plast Surg Clin North Am. 2018 Nov;26(4):415-424. doi: 10.1016/j.fsc.2018.06.003. Epub 2018 Aug 16. PMID: 30213423.

Ralf Paus, Kerstin Foitzik, In search of the “hair cycle clock”: a guided tour, Differentiation, Volume 72, Issues 9–10, 2004, Pages 489-511, ISSN 0301-4681, https://doi.org/10.1111/j.1432-0436.2004.07209004.x.

Hanna Wosicka, Krzysztof Cal, Targeting to the hair follicles: Current status and potential, Journal of Dermatological Science, Volume 57, Issue 2, 2010, Pages 83-89, ISSN 0923-1811, https://doi.org/10.1016/j.jdermsci.2009.12.005.

Van Neste D, Leroy T, Conil S. Exogen hair characterization in human scalp. Skin Res Technol. 2007 Nov;13(4):436-43. doi: 10.1111/j.1600-0846.2007.00248.x. PMID: 17908196.

Jeff Donovan, MD, PhD, Beth G Goldstein, MD, Adam O Goldstein, MD, MPH. Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed on April 12, 2025. https://www.uptodate.com/contents/male-pattern-hair-loss-androgenetic-alopecia-in-males-pathogenesis-clinical-features-and-diagnosis

Ho CH, Sood T, Zito PM. Androgenetic Alopecia. [Updated 2024 Jan 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430924/

Ntshingila S, Oputu O, Arowolo AT, Khumalo NP. Androgenetic alopecia: An update. JAAD Int. 2023 Jul 22;13:150-158. doi: 10.1016/j.jdin.2023.07.005. PMID: 37823040; PMCID: PMC10562178.

Andrew G Messenger, MD, FRCPBrittany G Craiglow, MD. Alopecia areata: Clinical manifestations and diagnosis. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed on April 12, 2025. https://www.uptodate.com/contents/alopecia-areata-clinical-manifestations-and-diagnosis

Jakub Gołąb, Witold Lasek, Marek Jakóbisiak, Tomasz Stokłosa. Immunologia. Wydanie 6, Warszawa 2014. Wydawnictwo Naukowe PWN SA

Zhou, C., Li, X., Wang, C. et al. Alopecia Areata: an Update on Etiopathogenesis, Diagnosis, and Management. Clinic Rev Allerg Immunol 61, 403–423 (2021). https://doi.org/10.1007/s12016-021-08883-0

Nagasawa T. CXC chemokine ligand 12 (CXCL12) and its receptor CXCR4. J Mol Med (Berl). 2014 May;92(5):433-9. doi: 10.1007/s00109-014-1123-8. Epub 2014 Apr 11. PMID: 24722947.

Britton C, Poznansky MC, Reeves P. Polyfunctionality of the CXCR4/CXCL12 axis in health and disease: Implications for therapeutic interventions in cancer and immune-mediated diseases. FASEB J. 2021 Apr;35(4):e21260. doi: 10.1096/fj.202001273R. PMID: 33715207.

Gordana Timotijević, Marija Mostarica Stojković, Djordje Miljković, CXCL12: Role in neuroinflammation, The International Journal of Biochemistry & Cell Biology, Volume 44, Issue 6, 2012, Pages 838-841, ISSN 1357-2725, https://doi.org/10.1016/j.biocel.2012.03.014.

L. Michel, P. Reygagne, P. Benech, F. Jean‐Louis, S. Scalvino, S. Ly Ka So, Z. Hamidou, S. Bianovici, J. Pouch, B. Ducos, M. Bonnet, A. Bensussan, A. Patatian, E. Lati, J. Wdzieczak‐Bakala, J‐C. Choulot, E. Loing, M. Hocquaux, Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways, British Journal of Dermatology, Volume 177, Issue 5, 1 November 2017, Pages 1322–1336, https://doi.org/10.1111/bjd.15577

Mei Zheng, Sang Ho Oh, Nahyun Choi, Yong Jin Choi, Jino Kim, Jong-Hyuk Sung, CXCL12 inhibits hair growth through CXCR4, Biomedicine & Pharmacotherapy, Volume 150, 2022, 112996, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2022.112996.

Zheng M, Kim MH, Park SG, Kim WS, Oh SH, Sung JH. CXCL12 Neutralizing Antibody Promotes Hair Growth in Androgenic Alopecia and Alopecia Areata. Int J Mol Sci. 2024 Jan 30;25(3):1705. doi: 10.3390/ijms25031705. PMID: 38338982; PMCID: PMC10855715.

Jeff Donovan, MD, PhD, Beth G Goldstein, MD, Adam O Goldstein, MD, MPH. Male pattern hair loss (androgenetic alopecia in males): Management. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed on April 12, 2025.

Freitas E, Guttman-Yassky E, Torres T. Baricitinib for the Treatment of Alopecia Areata. Drugs. 2023 Jun;83(9):761-770. doi: 10.1007/s40265-023-01873-w. Epub 2023 May 17. PMID: 37195491; PMCID: PMC10191081.

Schust J, Sperl B, Hollis A, Mayer TU, Berg T. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem Biol. 2006 Nov;13(11):1235-42. doi: 10.1016/j.chembiol.2006.09.018. PMID: 17114005.

Zheng M, An S, Park IG, Kim J, Kim WS, Noh M, Sung JH. Differential Expression of CXCL12 in Human and Mouse Hair: Androgens Induce CXCL12 in Human Dermal Papilla and Dermal Sheath Cup. Int J Mol Sci. 2024 Dec 26;26(1):95. doi: 10.3390/ijms26010095. PMID: 39795953; PMCID: PMC11719931.

Cockshott ID. Bicalutamide: clinical pharmacokinetics and metabolism. Clin Pharmacokinet. 2004;43(13):855-78. doi: 10.2165/00003088-200443130-00003. PMID: 15509184.

An S, Zheng M, Park IG, Park SG, Noh M, Sung JH. Humanized CXCL12 antibody delays onset and modulates immune response in alopecia areata mice: insights from single-cell RNA sequencing. Front Immunol. 2024 Oct 17;15:1444777. doi: 10.3389/fimmu.2024.1444777. PMID: 39483478; PMCID: PMC11524852.