Expression ofSfrp2Is Increased in Catagen of Hair Follicles and Inhibits Keratinocyte Proliferation

Abstract

BackgroundHair follicles undergo cycles of repeated growth and regression. The Wnt pathway plays an important role in the regeneration and differentiation of hair follicles. Sfrp2, a Wnt inhibitor, is involved in the developmental and disease processes of various cells and tissues by modulating the Wnt pathway.ObjectiveThe aim of this study was to understand the role of Sfrp2 in hair follicles through investigation of the Sfrp2 expression pattern in the skin and its effect on keratinocytes.MethodsWe investigated Sfrp2 mRNA expression and the expression of the wnt target genes, Ccnd1 and C-myc, at various mouse hair follicle developmental stages using Real-time polymerase chain reaction. We also investigated the effect of SFRP2 on the proliferation and differentiation of mouse keratinocyte cells by adding SFRP2 protein or overexpressing Sfrp2 using an in vitro culture system.ResultsSfrp2 expression peaked in the catagen phase and remained high until telogen, and then declined at the beginning of the next anagen. An inverse relationship to Sfrp2 expression was found for the expression of the Wnt target genes, C-myc and Ccnd1. In addition, we also observed inhibited proliferation of mouse keratinocytes in the presence of SFRP2.ConclusionThese results suggest that Sfrp2 may play a role in the catagen phase by inhibiting the proliferation of keratinocyte and functioning as a Wnt inhibitor in keratinocytes.

Secreted Frizzled-Related Protein 2 (sFRP2) Functions as a Melanogenic Stimulator; the Role of sFRP2 in UV-Induced Hyperpigmentary Disorders

“…In the skin, the role of sFRP2 was previously observed during the epithelial-mesenchymal interaction in the hair follicle (Kim and Yoon, 2014;Rendl et al, 2005). It was shown that sFRP2 is expressed in the dermal papilla and in the matrix of hair follicles (Rutberg et al, 2006).…”

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways

“…While DKK1 expression remained unchanged in our study, expression of SFRP2 was significantly increased in > 80% of our patients with AGA ( P < 0·002). SFRP2 , expressed in the epithelial portion of HFs, has been shown to be involved in hair fibre differentiation, and in the catagen phase by inhibiting keratinocyte differentiation …”

Characterization and functional analysis of SIAH1 during skin and hair follicle development in the angora rabbit (Oryctolagus cuniculus)

“…Skin and hair follicle development-related genes play different roles at the various stages of hair follicle development. For example, SFRP2 is principally expressed during the degenerative phase [8]. DDK1 is an inhibitor of the classical Wnt signaling pathway and is mainly expressed during the growth phase [32].…”

“…FGF2 promotes the proliferation of dermal papillae and mitosis of true skin fibroblasts [35]. During catagen of hair follicles, SFRP2 affects skin and hair follicle development by inhibition of keratinocyte proliferation and Wnt activity [8] and DKK1 has been shown to promote the regression of hair follicles [37]. The expression levels of all these genes changed significantly after overexpression of SIAH1.…”

“…Dermal hair papilla cells can be used as a cell model to study hair follicle growth and periodic changes. A number of studies have revealed that different genes have either a promoting or inhibitory effect on skin and hair follicle development, including hepatocyte growth factor (HGF), heat shock protein 27 (HSP27), secreted frizzled-related protein 4 (SFRP2) and fibroblast growth factor 5 (FGF5) [6][7][8][9]. Previously, differentially expressed genes (DEGs) related to hair follicle cycling were identified by Illumina sequencing in skin samples from different stages of skin and hair follicle developmental in Angora rabbits, including BMP2, KRT17, HTATIP2 and SIAH1 [10].…”