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

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Misaki Kinoshita-Ise ◽  
Aki Tsukashima ◽  
Tomonari Kinoshita ◽  
Yoshimi Yamazaki ◽  
Manabu Ohyama

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.

2019 ◽  
Vol 103 (5) ◽  
pp. 1602-1609
Author(s):  
Liya Bai ◽  
Shuxia Gao ◽  
Haitao Sun ◽  
Xueyan Zhao ◽  
Liping Yang ◽  
...  

2022 ◽  
Vol 65 (1) ◽  
pp. 11-19
Author(s):  
Yu Cui ◽  
Chunliang Wang ◽  
Lirong Liu ◽  
Nan Liu ◽  
Jianning He

Abstract. The objective of this study was to identify the expression and distribution of EPHA4 and Ephrin A3 genes in the development and morphogenesis of hair follicles in fine-wool sheep. The results could lay a theoretical basis for understanding the molecular mechanism that regulates hair follicle development. The skin of Aohan fine-wool sheep at different developmental stages (embryonic day 90, E90d, and 120, E120d, and postnatal day 1, B1d, and 30, B30d) were selected. Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were used to study the levels of mRNA and proteins, respectively. The RT-qPCR results showed that the mRNA expression level of EPHA4 at B1d was significantly lower than at E120d (p<0.01). The expression of Ephrin A3 at E120d was significantly higher than that at E90d and B1d (p<0.01). Immunohistochemical detection results showed that the level and localisation of EPHA4 and Ephrin A3 proteins had spatial and temporal specificity. EPHA4 expression in dermal papilla cells might be important for inducing Aohan fine-hair follicle regeneration and for controlling the properties of the hair. Ephrin A3 might play an important role in the redifferentiation of secondary hair follicles and might also be involved in the inhibition of apoptosis-related gene expression in hair follicles. The Ephrin A3 signalling pathway might accelerate the growth of fine-hair follicles and increase the density of hair follicles.


2020 ◽  
Vol 21 (12) ◽  
pp. 4553
Author(s):  
Sung Min Kim ◽  
Jung-Il Kang ◽  
Hoon-Seok Yoon ◽  
Youn Kyung Choi ◽  
Ji Soo Go ◽  
...  

The hair follicle goes through repetitive cycles including anagen, catagen, and telogen. The interaction of dermal papilla cells (DPCs) and keratinocytes regulates the hair cycle and hair growth. Humanin was discovered in the surviving brain cells of patients with Alzheimer’s disease. HNG, a humanin analogue, activates cell growth, proliferation, and cell cycle progression, and it protects cells from apoptosis. This study was performed to investigate the promoting effect and action mechanisms of HNG on hair growth. HNG significantly increased DPC proliferation. HNG significantly increased hair shaft elongation in vibrissa hair follicle organ culture. In vivo experiment showed that HNG prolonged anagen duration and inhibited hair follicle cell apoptosis, indicating that HNG inhibited the transition from the anagen to catagen phase mice. Furthermore, HNG activated extracellular signal-regulated kinase (Erk)1/2, Akt, and signal transducer and activator of transcription (Stat3) within minutes and up-regulated vascular endothelial growth factor (VEGF) levels on DPCs. This means that HNG could induce the anagen phase longer by up-regulating VEGF, which is a Stat3 target gene and one of the anagen maintenance factors. HNG stimulated the anagen phase longer with VEGF up-regulation, and it prevented apoptosis by activating Erk1/2, Akt, and Stat3 signaling.


2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Ningxia Zhu ◽  
Keng Huang ◽  
Yang Liu ◽  
Huan Zhang ◽  
En Lin ◽  
...  

Dermal papilla (DP) cells play a vital role in hair follicle (HF) development and postnatal hair cycling. However, the abilities are lost on further culture. Recent studies have demonstrated significant influences of posttranscriptional regulation by microRNA (miRNA) on HF development. The current study aims to investigate how miRNAs regulate Wnt/β-catenin to control HF inductivity of DP cells by performing microarray analysis in early- and late-passage DP cells and transfecting with miRNAs inhibitor or mimic. Results showed early-passage DP cells strongly expressed miRNAs related to inhibition of noncanonical Wnt pathways. In late-passage DP cells, miRNAs capable of inhibiting the canonical Wnt/β-catenin pathway were upregulated, in addition to the miRNAs targeting the noncanonical Wnt pathway. Moreover, we verified that β-catenin expression was downregulated by miR-195-5p overexpression in dose manner. Meanwhile LRP6 expression was downregulated in both protein and mRNA as well as the genes involved in the hair inductivity of DP cells. These results suggest that the appearance of miRNAs that suppress the Wnt/β-catenin pathway may be responsible for the loss of ability of DP cells in culture and miR-195-5p is the potential key factor involved in regulating HF inductivity of DP cells.


Development ◽  
1984 ◽  
Vol 79 (1) ◽  
pp. 211-224
Author(s):  
Colin A. B. Jahoda ◽  
Roy F. Oliver

Parallel cultures of adult rat vibrissa dermal papilla cells and skin fibroblasts revealed differences between the two cell types with respect to a number of criteria. In particular the dermal papilla cells demonstrated a distinctive single cell morphology, and at confluence formed cell aggregates radically different from regular fibroblast multilayering and patterning. This finding confirmed repeated observations of papilla cell clumping in short-term culture. The dermal papilla cells which are mitotically quiescent in situ were also shown to have a lower proliferative capacity than the skin fibroblasts. The affinity shown by papilla cells towards each other in culture reflected the behaviour demonstrated by isolated dermal papillae transplanted into ear dermis and into the collagenous capsule of the vibrissa follicle. In the absence of epidermal contact the papilla cells remained as recognizable rounded aggregates for the experimental period of up to nine months. Synthesis of extracellular material typical of that seen in situ was observed, particularly during the first weeks following transplantation. The collective behaviour of the dermal papilla cells revealed in this study may be significant for the morphogenetic activity of the papilla, and for papilla size during the hair cycle. It may also reflect the retention of embryonic-like properties by the dermal component of adult hair follicles.


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