Abstract
BackgroundHair follicle (HF) formation and growth are sustained by epithelial-mesenchymal interaction via growth factors and cytokines. Pivotal roles of FGFs on HF regeneration and neogenesis have been reported mainly in rodent models. FGF expression is regulated by upstream pathways, represented by canonical WNT signaling; however, how FGFs influence on human folliculogenesis remains elusive. The aim of this study is to assess if human scalp-derived fibroblasts (sFBs) are able to modulate their FGF expression profile in response to WNT activation and to evaluate the influence of WNT-activated or suppressed FGFs on folliculogenesis.MethodsDermal papilla cells (DPCs), dermal sheath cells (DSCs), and sFBs were isolated from the human scalp and cultured independently. The gene expression profile of FGFs in DPCs, DSCs, and sFBs and the influence of WNT activator, CHIR99021, on FGF expression pattern in sFBs were evaluated by reverse transcription polymerase chain reaction, which were confirmed at protein level by western blotting analysis. The changes in the expression of DPC or keratinocyte (KC) biomarkers under the presence of FGF7 or 9 were examined in both single and co-culture assay of DPCs and/or KCs. The influence of FGF 7 and FGF 9 on hair morphogenesis and growth was analyzed in vivo using mouse chamber assay.ResultsIn single culture, sFBs were distinguished from DPCs and DSCs by relatively high expression of FGF5 and FGF18, potential inducers of hair cycle retardation or catagen phase. In WNT-activated state, sFBs downregulated FGF7 while upregulating FGF9, a positive regulator of HF morphogenesis, FGF16 and FGF20 belonging to the same FGF subfamily. In addition, CHIR99021, a WNT activator, dose-dependently modulated FGF7 and 9 expression to be folliculogenic. Altered expressions of FGF7 and FGF9 by CHIR99021 were confirmed at protein level. Supplementation of FGF9 to cultured DPCs resulted in upregulation of representative DP biomarkers and this tendency was sustained, when DPCs were co-cultured with KCs. In mouse chamber assay, FGF9 increased both the number and the diameter of newly formed HFs, while FGF7 decreased HF diameter.ConclusionThe results implied that sFBs support HF formation by modulating regional FGF expression profile responding to WNT activation.
Highlights
Hair follicle (HF) formation and growth are sustained by epithelial-mesenchymal interaction via growth factors and cytokines
The results implied that Scalp-derived fibroblast (sFB) support HF formation by modulating regional FGF expression profile responding to WNT activation
A recent study suggested that fibroblast growth factor 9 (FGF9) secreted from perifollicular dermal fibroblasts in response to upstream WNT activation plays a key role in the wound-induced model of HF neogenesis in mouse [5]
Summary
Hair follicle (HF) formation and growth are sustained by epithelial-mesenchymal interaction via growth factors and cytokines. A recent study suggested that fibroblast growth factor 9 (FGF9) secreted from perifollicular dermal fibroblasts in response to upstream WNT activation plays a key role in the wound-induced model of HF neogenesis in mouse [5]. Mammalian FGF is comprised of 23 factors and can be subdivided into 7 subfamilies based on its structural similarity, biochemical functions, and evolutionary relationships [7]. Considering their diversity, it is reasonable to speculate that identical molecules may exhibit respective roles in other species. Past studies mainly adopted murine knockout models, allowing the functional dissection of limited number of FGFs. Whether human dermal fibroblasts, especially those residing in the scalp dermis, produce FGFs, let alone their FGF production profiles, is still ill-investigated. We attempted to investigate, firstly, if human scalpderived dermal fibroblasts (sFBs) are able to express
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