Altered FGF expression profile in human scalp-derived fibroblasts upon WNT activation: implication of their role to provide folliculogenetic microenvironment

Abstract

Background Hair 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. Methods Dermal 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. Results In 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. Conclusion The results implied that sFBs support HF formation by modulating regional FGF expression profile responding to WNT activation.

Acute Glycogen Synthase Kinase-3 Inhibition Modulates Human Cardiac Conduction

“…Interestingly, we determined that SCN5A was not decreased, indicating mechanism(s) independent of transcription underlying the protein level change with acute SB2 treatment ( Figure 4B ). FGF12 , the human homolog of mouse Fgf13 that encodes for fibroblast growth factor 13, has been shown to be down-regulated by Wnt activation 52 and has been previously shown to directly modulate sodium current density. 53 Therefore, we asked whether this gene is altered by acute GSK-3 inhibition.…”

Cost-effectively dissecting the genetic architecture of complex wool traits in rabbits by low-coverage sequencing

“…The most significant locus (chr11: 65,412,003 bp, P = 1.42E-11) associated with fine fiber was detected closest to the FGF10 gene (chr11: 64,989,932-65,080,400) that was also the nearest gene to the QTL for DFW (chr11: 64,944,841-64,952,273). Fibroblast growth factor 10 ( FGF10 ) is a member of the fibroblast growth factor (FGF) family possessing broad mitogenic and cell survival activities and famous for regulation of hair morphogenesis and cycle hair growth in human and mice (Greco et al, 2009, Kinoshita-Ise et al, 2020).…”

“…In addition, FGFs might play an important role in hair morphogenesis. For example, FGF2 (Takabayashi et al, 2016), FGF7 (Seo et al, 2016), FGF9 (Kinoshita-Ise et al, 2020), FGF10 (Schlake, 2005) and so on have been studied to contribute to a different fiber diameter in human and mice. What’s more, FGF7 and FGF10 efficiently and specifically bind to FGFR2-IIIb, one of several diverse protein variants with distinct binding characteristics encoded by the FGFR2 gene.…”

Promoter Methylation Changes in KRT17: A Novel Epigenetic Marker for Wool Production in Angora Rabbit

“…Next, we analyzed the expression of KRT17 . Using a rabbit hair follicle development synchronization model, we found that KRT17 expression exhibited periodicity with hair follicle development, and KRT17 regulated WNT signaling pathway genes, such as WNT2 [ 15 ], FGF2 [ 16 ], TGFβ [ 17 ], SFRP2 [ 18 , 19 ], BMP2 [ 20 ], etc. This suggested that KRT17 could affect the transcription of hair follicle development-related genes playing a positive regulatory role in inducing the transition of hair follicles from telogen to anagen.…”