Cyclosporin A-induced hair growth in mice is associated with inhibition of
calcineurin-dependent activation of NFAT in follicular keratinocytes.
Gafter-Gvili, Anat, Benjamin Sredni, Rivka Gal, Uzi Gafter, and Yona Kalechman.
1Departments of Nephrology and Pathology, Rabin Medical Center, Petah Tikva,
49372; Sackler School of Medicine, Tel Aviv University, Tel Aviv; and 2C.A.I.R.
Institute, Faculty of Life Sciences, Bar Ilan University, Ramat Gan, 52900 Israel
APStracts 10:0078C, 2003.
One of the most common side effects of treatment with cyclosporin A (CsA) is
hypertrichosis. This study shows that calcineurin activity is associated with hair
keratinocyte differentiation in vivo, affecting nuclear factor of activated T cells (NFAT1)
activity in these cells. Treatment of nude or C57BL/6 depilated normal mice with CsA
inhibited the expression of keratinocyte terminal differentiation markers associated with
catagen, along with the inhibition of calcineurin and NFAT1 nuclear translocation. This
was associated with induction of hair growth in nude mice and retardation of spontaneous
catagen induction in depilated normal mice. Furthermore, calcineurin inhibition blocked
the expression of p21waf/cip1 and p27kip1, which are usually induced with
differentiation. This was also associated with an increase in interleukin-1a expression
(nude mice), a decrease in transforming growth factor-ß (nude and normal mice), and no
change in keratinocyte growth factor expression in the skin. Retardation of catagen in
CsA-treated mice was accompanied by significant alterations in apoptosis-related gene
product expression in hair follicle keratinocytes. The ratio of the anti-apoptotic Bcl-2 to
proapoptotic Bax expression increased, and expression of p53 and ICE activity
decreased. These data provide the first evidence that calcineurin is functionally active in
follicular keratinocytes and that inhibition of the calcineurin-NFAT1 pathway in these
cells in vivo by CsA enhances hair growth.
Received 19 November 2002; accepted in final form 10 February 2003
APS Manuscript Number C537-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003