Adenosine Stimulates Fibroblast Growth Factor-7 Gene Expression Via Adenosine A2b Receptor Signaling in Dermal Papilla Cells

Iino, Masato; Ehama, Ritsuko; Nakazawa, Yosuke; Iwabuchi, Tokuro; Ogo, Masashi; Tajima, Masahiro; Arase, Seiji

doi:10.1038/sj.jid.5700728

Cited by 74 publications

(65 citation statements)

References 30 publications

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“…It stimulates VEGF production through activation of cell surface adenosine receptors, and this adenosine-mediated signal transduction pathway contributes to minoxidil-induced hair growth (9). Gene expression of FGF-7 was up-regulated by adenosine treatment in DP cells (10). Oura et al (17) demonstrated that adenosine significantly increased the anagen hair growth rate and the thickness of hair in a human clinical study.…”

Section: Discussionmentioning

confidence: 99%

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Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles

Hwang

Kim²,

Roh³

et al. 2011

Int J Mol Med

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Abstract. Hair regression and balding are distressing concerns for an increasing number of people due to changes in lifestyle and serious nutritional imbalances. Therapies for treatment of hair loss are needed. Among potential therapeutics, adenosine has been suggested as a potent regulator of hair growth. In this study, we investigated the effects of adenosine on hair follicles and dermal papilla (DP) cells, and the mechanism underlying the action of adenosine. Hair follicles are organs, including DP cells, that are responsible for the production of hair fibers by inducing and maintaining the hair growth phase (anagen). In a culture of DP cells in vitro, adenosine stimulated proliferation of DP cells by increasing thymidine uptake. Subsequently, adenosine activated and elongated the anagen phase by increasing the uptake of radiolabeled cysteine in an organ culture of mouse vibrissae hair follicles. We also confirmed that adenosine promoted the expression of several growth factors that are responsible for hair growth, including fibroblast growth factors (FGF)-7, FGF-2, insulin-like growth factor (IGF)-1, and vascular endothelial growth factor (VEGF) in a cDNA microarray with semi-quantitative RT-PCR. Transcriptional activation of β-catenin in DP cells was increased by adenosine in a luciferase assay. β-catenin is a co-activator of Wnt/β-catenin signaling that induces morphogenesis and differentiation of hair follicles and also acts to transactivate downstream signaling pathways, including the ERK pathway. Using Western blotting, we found that adenosine stimulated phosphorylation of ERK, CREB and AKT. These results suggest that adenosine stimulates growth of hair follicles by triggering the expression of growth factors and β-catenin, and by inducing their downstream target signaling pathways.

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Section: Discussionmentioning

confidence: 99%

“…Li et al (9) proposed an adenosine mediated mechanism for minoxidil-induced vascular endothelial growth factor (VEGF) production by the signaling pathway. Iino et al (10) reported that adenosine stimulates FGF-7 gene expression. However, the potential effects of adenosine on hair growth have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles

Hwang

Kim²,

Roh³

et al. 2011

Int J Mol Med

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“…Among these FGF genes, FGF-7 was found to be expressed in the hair follicle. FGF-7 RNA is localized to the dermal papilla during anagen, but expression is down-regulated by the lateanagen VI stage [22]. Besides, no FGF-7 RNA was detected in follicles during catagen or telogen [23].…”

Section: Real-time Pcr (Qpcr)mentioning

confidence: 94%

In <i>Vitro</i> Effects of the Phytocomplex TrichoTech<sup>TM</sup> on Human Fibroblasts: Proliferative Potential and Effects on Gene Expression of FGF-7 and FGF-10

Amaral¹,

Jardim²,

Antunes³

et al. 2017

JCDSA

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The human hair follicle, a mini-organ formed with neuroectodermal-mesodermal interaction, is a complex structure, in the active steady state (anagen) the dermal papilla can be considered as a ball of extracellular matrix, surrounding specialized fibroblasts. The cross-talk of dermal papilla with neighbouring matrix cells results in the maintenance of hair fibre production. This study aimed to investigate the proliferative potential of the compound Trichotech TM , a phytocomplex obtained from a mixture of essential oils, on cultured human fibroblasts and its ability to modulate the gene expression of FGF-7 and FGF-10. Trichotech TM was shown to enhance fibroblasts proliferation in concentrations of 0.5% to 2.0%, and also increase the percentage of cells in the S/G2/M phases of the cell cycle. Trichotech TM at both 1.0% and 2.0% induced a statistically significant effect on wound healing assay compared to the untreated control. We examined the interaction between cell survival (PI3K/Akt) and mitogenic (Ras/MAPK) signal transduction pathways after Trichotech TM treatment (1.0% and 2.0%) on the fibroblast cell line.

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“…Studies performed by the Shiseido Research Group indicate that adenosine, via A 2B AR, might stimulate hair growth through fibroblast growth factor-7 gene expression upregulation in dermal papilla cells [57].…”

Section: Therapeutic Potential Of a 2b Adenosine Receptor Agonistsmentioning

confidence: 99%

Recent improvements in the development of A2B adenosine receptor agonists

Baraldi

Tabrizi²,

Fruttarolo³

et al. 2009

Purinergic Signalling

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Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A 1 , A 2A , A 2B and A 3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A 2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A 2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A 2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleosidebased agonists are the result of modifying adenosine by substitution at the N 6 -, C 2 -positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-and its 2-chloro analogue 23 (hA 1 K i =3500 nM, hA 2A K i = 4950 nM, hA 2B EC 50 =210 nM, hA 3 K i >5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA 2B AR.Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3, 5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60-6583, hA 1 , hA 2A , hA 3 EC 50 >10 μM; hA 2B EC 50 =3 nM) is currently under preclinicalphase investigation for treating coronary artery disorders and atherosclerosis.

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Adenosine Stimulates Fibroblast Growth Factor-7 Gene Expression Via Adenosine A2b Receptor Signaling in Dermal Papilla Cells

Cited by 74 publications

References 30 publications

Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles

Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles

In <i>Vitro</i> Effects of the Phytocomplex TrichoTech<sup>TM</sup> on Human Fibroblasts: Proliferative Potential and Effects on Gene Expression of FGF-7 and FGF-10

Recent improvements in the development of A2B adenosine receptor agonists

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Adenosine Stimulates Fibroblast Growth Factor-7 Gene Expression Via Adenosine A2b Receptor Signaling in Dermal Papilla Cells

Cited by 74 publications

References 30 publications

Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles

Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles

In &lt;i&gt;Vitro&lt;/i&gt; Effects of the Phytocomplex TrichoTech&lt;sup&gt;TM&lt;/sup&gt; on Human Fibroblasts: Proliferative Potential and Effects on Gene Expression of FGF-7 and FGF-10

Recent improvements in the development of A2B adenosine receptor agonists

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In <i>Vitro</i> Effects of the Phytocomplex TrichoTech<sup>TM</sup> on Human Fibroblasts: Proliferative Potential and Effects on Gene Expression of FGF-7 and FGF-10