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Int. J. Mol. Sci. 2014, 15(9), 16800-16815; doi:10.3390/ijms150916800

Mycophenolate Antagonizes IFN-γ-Induced Catagen-Like Changes via β-Catenin Activation in Human Dermal Papilla Cells and Hair Follicles

1
Department of Dermatology, Chung-Ang University College of Medicine, Seoul 137-701, Korea
2
Department of Medicine, the Graduate School, Chung-Ang University, Seoul 137-701, Korea
3
Department of Dermatology, St. Paul's Hospital, College of Medicine, the Catholic University of Korea, Seoul 137-701, Korea
4
Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul 137-701, Korea
5
Department of Dermatology, Denver Health Medical Center, Denver, CO 80204, USA
6
Department of Dermatology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
7
Department of Dermatology, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 20 June 2014 / Revised: 23 August 2014 / Accepted: 3 September 2014 / Published: 22 September 2014
(This article belongs to the Special Issue Pharmaceuticals and Nutraceuticals by Molecular Farming)
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Abstract

Recently, various immunosuppressant drugs have been shown to induce hair growth in normal hair as well as in alopecia areata and androgenic alopecia; however, the responsible mechanism has not yet been fully elucidated. In this study, we investigate the influence of mycophenolate (MPA), an immunosuppressant, on the proliferation of human dermal papilla cells (hDPCs) and on the growth of human hair follicles following catagen induction with interferon (IFN)-γ. IFN-γ was found to reduce β-catenin, an activator of hair follicle growth, and activate glycogen synthase kinase (GSK)-3β, and enhance expression of the Wnt inhibitor DKK-1 and catagen inducer transforming growth factor (TGF)-β2. IFN-γ inhibited expression of ALP and other dermal papillar cells (DPCs) markers such as Axin2, IGF-1, and FGF 7 and 10. MPA increased β-catenin in IFN-γ-treated hDPCs leading to its nuclear accumulation via inhibition of GSK3β and reduction of DKK-1. Furthermore, MPA significantly increased expression of ALP and other DPC marker genes but inhibited expression of TGF-β2. Therefore, we demonstrate for the first time that IFN-γ induces catagen-like changes in hDPCs and in hair follicles via inhibition of Wnt/β-catenin signaling, and that MPA stabilizes β-catenin by inhibiting GSK3β leading to increased β-catenin target gene and DP signature gene expression, which may, in part, counteract IFN-γ-induced catagen in hDPCs. View Full-Text
Keywords: MPA; β-catenin; GSK3β; DKK-1; IFN-γ; TGF-β2; dermal papilla cell; hair growth MPA; β-catenin; GSK3β; DKK-1; IFN-γ; TGF-β2; dermal papilla cell; hair growth
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MDPI and ACS Style

Ryu, S.; Lee, Y.; Hyun, M.Y.; Choi, S.Y.; Jeong, K.H.; Park, Y.M.; Kang, H.; Park, K.Y.; Armstrong, C.A.; Johnson, A.; Song, P.I.; Kim, B.J. Mycophenolate Antagonizes IFN-γ-Induced Catagen-Like Changes via β-Catenin Activation in Human Dermal Papilla Cells and Hair Follicles. Int. J. Mol. Sci. 2014, 15, 16800-16815.

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