Progressive expression of PPARGC1\u03b1 is associated with hair miniaturization in androgenetic alopecia

Bryan Siu-Yin Ho,Axel Hillmer,Candida Vaz,Huma Jaffar,Srinivas Ramasamy,Paul Lorenz Bigliardi,Vivek Tanavde,Jameelah Sheik Mohamed,Mei Bigliardi-Qi,Elaine Guo Yan Chew

doi:10.1038/s41598-019-43998-7

Abstract

Current opinion views androgens as the pathogenic driver in the miniaturization of hair follicles of androgenetic alopecia by interfering with the dermal papilla. This cannot be the sole cause and therefore it is important for therapeutic and diagnostic purposes to identify additional pathways. Comparative full transcriptome profile analysis of the hair bulb region of normal and miniaturized hair follicles from vertex and occipital region in males with and without androgenetic alopecia revealed that next to the androgen receptor as well the retinoid receptor and particularly the PPAR pathway is involved in progressive hair miniaturization. We demonstrate the concurrent up-regulation of PPARGC1a in the epithelial compartment and androgen receptor in the dermal papilla of miniaturized hair. Dynamic Ppargc1a expression in the mouse hair cycle suggests a possible role in regulating hair growth and differentiation. This is supported by reduced proliferation of human dermal papilla and predominantly epithelial keratinocytes after incubation with AICAR, the agonist for AMPK signaling which activates PPARGC1a and serves as co-activator of PPARγ. In addition, miRNA profiling shows enrichment of miRNA-targeted genes in retinoid receptors and PPARGC1α/PPARγ signaling, and antigen presentation pathways.

Highlights

Male patterned hair loss, or androgenetic alopecia (AGA) is the most common form of hair loss, prominent in males and characterized by progressive miniaturization of hair follicles[1]
PPAR is controlling fatty acid metabolism and its up-regulation in hair bulb was closely related to hair miniaturization and concurrent androgen receptor (AR) up-regulation
The progressive nature of hair miniaturization in AGA has been demonstrated with the discovery of intermediate hair follicles which presents altered morphology[33]

Summary

Introduction

Androgenetic alopecia (AGA) is the most common form of hair loss, prominent in males and characterized by progressive miniaturization of hair follicles[1]. Regulators of energy metabolism and inflammation such as the nuclear Peroxisome proliferator-activated receptors (PPARγ, α, β) are involved in hair loss[12]. In an anagen human hair follicle PPARγ expression is detected in the mesenchymal DP cells, epithelial cells of the outer root sheath (ORS), inner root sheath and matrix[16]. We show the up-regulation of PGC1a in the inner and outer root sheath (IRS/ORS) of hair follicles from AGA patients and the dynamic expression in the mouse hair cycle. The expression of PGC1a is concomitant with the AR up-regulation in miniaturized hair and indicates its involvement in hair development and pathogenesis of AGA. Characterization of miRNA expression profile provided support for AR, PPAR, retinoic acid signaling and inflammation in miniaturized hair

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Conclusion