Cyclosporin A-induced hair growth in mice is associated with inhibition of calcineurin-dependent activation of NFAT in follicular keratinocytes.

Abstract	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 p21(waf/cip1) and p27(kip1), which are usually induced with differentiation. This was also associated with an increase in interleukin-1alpha expression (nude mice), a decrease in transforming growth factor-beta (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 interleukin-1beta converting enzyme 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.
Authors	Anat Gafter-Gvili, Benjamin Sredni, Rivka Gal, Uzi Gafter, Yona Kalechman
Journal	American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 284 Issue 6 Pg. C1593-603 (Jun 2003) ISSN: 0363-6143 [Print] United States
PMID	12734112 (Publication Type: Journal Article)
Chemical References	BAX protein, human Bax protein, mouse CDKN1A protein, human Cdkn1a protein, mouse Cdkn1b protein, mouse Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p21 Cyclins DNA-Binding Proteins Immunosuppressive Agents NFATC Transcription Factors NFATC2 protein, human Nfatc2 protein, mouse Nuclear Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Transcription Factors Tumor Suppressor Protein p53 Tumor Suppressor Proteins bcl-2-Associated X Protein Cyclin-Dependent Kinase Inhibitor p27 Cyclosporine Calcineurin
Topics	Animals Calcineurin (metabolism) Cell Cycle Proteins (metabolism) Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Cyclins (metabolism) Cyclosporine (pharmacology) DNA-Binding Proteins (metabolism) Hair (growth & development) Hair Follicle (cytology, metabolism) Humans Hypertrichosis (metabolism) Immunosuppressive Agents (pharmacology) Keratinocytes (cytology, drug effects, metabolism) Mice Mice, Inbred C57BL Mice, Nude NFATC Transcription Factors Nuclear Proteins Proto-Oncogene Proteins (genetics, metabolism) Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism) Skin (anatomy & histology, metabolism) Transcription Factors (metabolism) Tumor Suppressor Protein p53 (genetics, metabolism) Tumor Suppressor Proteins (metabolism) bcl-2-Associated X Protein

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!