Transcriptional activation of CCN1 and CCN2, targets of canonical Wnt signal, by ascorbic acid 2-phosphate in human dermal papilla cells

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.

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l-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase

British Journal of Dermatology ◽

10.1111/j.1365-2133.2009.09108.x ◽

2009 ◽

Vol 160 (6) ◽

pp. 1157-1162 ◽

Cited By ~ 22

Author(s):

M.H. Kwack ◽

S.H. Shin ◽

S.R. Kim ◽

S.U. Im ◽

I.S. Han ◽

...

Keyword(s):

Ascorbic Acid ◽

Growth Factor ◽

Dermal Papilla ◽

Insulin Like Growth Factor ◽

Phosphatidylinositol 3 Kinase ◽

Dermal Papilla Cells ◽

Hair Shafts ◽

Phosphatidylinositol 3

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

Inflammation and Regeneration ◽

10.1186/s41232-020-00141-8 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Misaki Kinoshita-Ise ◽

Aki Tsukashima ◽

Tomonari Kinoshita ◽

Yoshimi Yamazaki ◽

Manabu Ohyama

Keyword(s):

Expression Profile ◽

Protein Level ◽

Dermal Papilla ◽

Dermal Papilla Cells ◽

Single Culture ◽

Activated State ◽

Polymerase Chain ◽

Canonical Wnt ◽

Hair Morphogenesis

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.

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