Efficacy of topical tofacitinib in promoting hair growth in non-scarring alopecia: possible mechanism via VEGF induction
- 650 Downloads
Tofacitinib is a Janus kinase 3 (JAK3) inhibitor that promotes hair growth; however, the efficacy and mechanism of this effect are not yet understood. This study aimed to evaluate the efficacy and mechanism of topical tofacitinib on hair growth in mice. Eight-week-old male C57BL/6 mice were divided equally into four groups and treated topically with tofacitinib, minoxidil, or vehicle once daily for 21 days. Weekly photographs were taken to determine the area and rate of hair growth, and tissue samples were collected for histopathological evaluation. mRNA and protein expression of anagen-maintaining growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), were determined via RT-PCR and ELISA, respectively. Tofacitinib-treated mice exhibited more hair regrowth than either minoxidil-treated or control mice did between day 7 and 21 (P < 0.05). Topical tofacitinib also promoted more rapid hair growth rate than topical minoxidil or control did (P < 0.001). Histopathology showed a distinct increase in the number of hair follicles, mostly in the anagen phase, in the tofacitinib-treated group. Hair follicles in the minoxidil- and vehicle-treated groups were more often classified as catagen and anagen. VEGF mRNA and protein expression in the tofacitinib-treated group was significantly greater than those in the other groups (P < 0.05). IGF-1 mRNA expression was not upregulated in tofacitinib-treated mice. Topical tofacitinib is effective in promoting hair growth, and the possible mechanism involves increased VEGF levels and lowered inflammation. This study will help develop a new therapeutic option for non-scarring alopecia.
KeywordsJAK3 inhibitor Non-scarring alopecia Hair growth VEGF IGF-1
The authors gratefully acknowledge the financial support provided by The Thailand Research Fund (Grant number: TRG6080021).
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest to declare.
- 2.Bachelez H, van de Kerkhof PCM, Strohal R, Kubanov A, Valenzuela F, Lee J-H, Yakusevich V, Chimenti S, Papacharalambous J, Proulx J, Gupta P, Tan H, Tawadrous M, Valdez H, Wolk R (2015) Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. Lancet 386:552–561CrossRefPubMedGoogle Scholar
- 4.Boy MG, Wang C, Wilkinson BE, Chow VF, Clucas AT, Krueger JG, Gaweco AS, Zwillich SH, Changelian PS, Chan G (2009) Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of CP-690,550 in patients with psoriasis. J Invest Dermatol 129:2299–2302CrossRefPubMedGoogle Scholar
- 15.Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, Warner JD, Tanaka M, Steward-Tharp SM, Gadina M, Thomas CJ, Minnerly JC, Storer CE, LaBranche TP, Radi ZA, Dowty ME, Head RD, Meyer DM, Kishore N, O’Shea JJ (2011) Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol 186:4234–4243CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, Price VH, Van Neste D, Roberts JL, Hordinsky M, Shapiro J, Binkowitz B, Gormley GJ (1998) Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol 39:578–589CrossRefPubMedGoogle Scholar
- 24.Kawano M, Komi-Kuramochi A, Asada M, Suzuki M, Oki J, Jiang J, Imamura T (2005) Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly expressed in hair follicles and capable of inducing anagen from telogen stage hair follicles. J Invest Dermatol 124:877–885CrossRefPubMedGoogle Scholar
- 36.Migita K, Izumi Y, Jiuchi Y, Kozuru H, Kawahara C, Izumi M, Sakai T, Nakamura M, Motokawa S, Nakamura T, Kawakami A (2014) Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis. Clin Exp Immunol 175:208–214CrossRefPubMedPubMedCentralGoogle Scholar
- 48.Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224CrossRefPubMedGoogle Scholar
- 49.van Gurp E, Weimar W, Gaston R, Brennan D, Mendez R, Pirsch J, Swan S, Pescovitz MD, Ni G, Wang C, Krishnaswami S, Chow V, Chan G (2008) Phase 1 Dose-Escalation Study of CP-690 550 in stable renal allograft recipients: preliminary findings of safety, tolerability, effects on lymphocyte subsets and pharmacokinetics. Am J Transplant 8:1711–1718CrossRefPubMedGoogle Scholar
- 50.Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L, Singh P, Petukhova L, Mackay-Wiggan J, Christiano AM, Clynes R (2014) Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 20:1043–1049CrossRefPubMedPubMedCentralGoogle Scholar