Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil.
Li M,
Marubayashi A,
Nakaya Y,
Fukui K,
Arase S.
Source
Department of Dermatology, School of Medicine, The University of Tokushima, Tokushima, Japan.
Abstract
The mechanism by which minoxidil, an adenosine-triphosphate-sensitive potassium channel opener, induces hypertrichosis remains to be elucidated. Minoxidil has been reported to stimulate the production of vascular endothelial growth factor, a possible promoter of hair growth, in cultured dermal papilla cells. The mechanism of production of vascular endothelial growth factor remains unclear, however.
We hypothesize that adenosine serves as a mediator of vascular endothelial growth factor production. Minoxidil-induced increases in levels of intracellular Ca(2+) and vascular endothelial growth factor production in cultured dermal papilla cells were found to be inhibited by 8-sulfophenyl theophylline, a specific antagonist for adenosine receptors, suggesting that dermal papilla cells possess adenosine receptors and sulfonylurea receptors, the latter of which is a well-known target receptor for adenosine-triphosphate-sensitive potassium channel openers. The expression of sulfonylurea receptor 2B and of the adenosine A1, A2A, and A2B receptors was detected in dermal papilla cells by means of reverse transcription polymerase chain reaction analysis. In order to determine which of the adenosine receptor subtypes contribute to minoxidil-induced hair growth, the effects of subtype-specific antagonists for adenosine receptors were investigated. Significant inhibition in increase in intracellular calcium level by minoxidil or adenosine was observed as the result of pretreatment with 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A1 receptor, but not by 3,7-dimethyl-1-propargyl-xanthine, an antagonist for adenosine A2 receptor, whereas vascular endothelial growth factor production was blocked by both adenosine A1 and A2 receptor antagonists. These results indicate that the effect of minoxidil is mediated by adenosine, which triggers intracellular signal transduction via both adenosine A1 and A2 receptors, and that the expression of sulfonylurea receptor 2B in dermal papilla cells might play a role in the production of adenosine.
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.123 A RANDOMIZED TRIAL OF ADENOSINE IN ANDROGENETIC ALOPECIA
Yasushi Watanabe, Kelshi Nagashima, Noriro Hanzawa, Masashl Ogo, Akihlro Ishino, Yosuke Nakazawa, Masaaki Uemura, and Masahiro Tajima
Watanabe Dermatological clinic, Tokyo, Shinjuku Biru Clinic, Tokyo, Shiseido Science division, Tokyo and Shiseido Research Center, Yokohama, Japan
Objective: Adenosine up-regulates the expression of fibroblast growth factor 7 (FGF7) and vascular endothelial growth factor (VEGF) on cultured dermal papilla cells via adenosine receptors. We therefore speculated that adenosine stimulates growth of hair fiber due to the action of FGF7 and VEGF for epithelial cells in hair follicles.
In this study,we performed a clinical trial to investigate the efficacy and safety of adenosine in hairloss associated with androgenetic alopecia (Androgenetic Alopecia).
Methods: Ahundred and four volunteers with AGAwere registered In a randomized double-blind trial that used an adenosine (0.7S%) topical lotion or niacin amide (0.1%)topical lotion twice daily for 6 months. Efficacy was evaluated by investigator assessments of change in global scalp coverage, change in the ratio of veilus-like(under 40 micrometers in diameter) and thick hairs (not less 60 micrometers or 80 micrometers in diameter), and hair density, in vertex.
Results: Fifty-one of 52 adenosine-treated subjects and 50 of 52 niacin amide-treated subjects completed the 6-month study. For global improvement, adenosine was significantly superior to niacin amide. Treatment with either lotion resulted in a significantlydecreased ratio of vellus- like hair and also significantly increased the ratio of thick hair, but did not change hair density. Regarding the Increase in the ratio of thick hair, adenosine was significantly superior to niacin amide. Adverse effects were not found.
Conclusion: In men with Androgenetic Alopecia,adenosine increased hair growth and thickened vellus-like hair without side effects. It would appear that the efficacy of hair growth results from the effects of FGF7 and VEGF which are stimulated by activation of adenosine receptors on dermal papilla cells.
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Intracellular adenosine triphosphate delivery enhanced skin wound healing in rabbits.Ann Plast Surg. 2009 Feb;62(2):180-6. doi: 10.1097/SAP.0b013e31817fe47e.
Intracellular adenosine triphosphate delivery enhanced skin wound healing in rabbits.
Wang J,
Zhang Q,
Wan R,
Mo Y,
Li M,
Tseng MT,
Chien S.
Source
Department of Surgery, University of Louisville School of Medicine, KY, USA.
j0wang19@louisville.edu
Abstract
Small unilamellar lipid vesicles were used to encapsulate adenosine triphosphate (ATP-vesicles) for intracellular energy delivery. This technique was tested in full-thickness skin wounds in 16 adult rabbits. One ear was rendered ischemic by using a minimally invasive surgery. The other ear served as a normal control. Four circular full-thickness wounds were created on the ventral side of each ear. ATP-vesicles or saline was used and the wounds were covered with Tegaderm (3M, St. Paul, MN). Dressing was changed and digital photos were taken daily until all the wounds were healed. The mean healing times of ATP-vesicles-treated wounds were significantly shorter than that of saline-treated wounds on ischemic and nonischemic ears. Histologic study indicated better-developed granular tissue and reepithelialization in the ATP-vesicles-treated wounds. The wounds treated by ATP-vesicles exhibited extremely fast granular tissue growth. More CD31 positive cells were seen in the ATP-vesicles-treated wounds. This preliminary study shows that direct intracellular delivery of ATP can accelerate the healing process of skin wounds on ischemic and nonischemic rabbit ears.
The extremely fast granular tissue growth was something never seen or reported in the past.
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Use of minoxidil for wound healing
Abstract
A method for the promotion or acceleration of wound healing by a treatment with minoxidil is disclosed. The minoxidial can be administered by topical application, oral administration, injection or any combination thereof. Treatment with minoxidil is effective for promoting the migration of epithelial cells in a wound or in tissues such as cornea and the like. Methods for identifying binding sites for minoxidil in cells based on their affinity for the compound in attachment or chemotactic assays are described.
http://www.google.ca/patents/US4912111
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J Dermatol. 2008 Dec;35(12):763-7. doi: 10.1111/j.1346-8138.2008.00564.x.
Adenosine increases anagen hair growth and thick hairs in Japanese women with female pattern hair loss: a pilot, double-blind, randomized, placebo-controlled trial.
Oura H,
Iino M,
Nakazawa Y,
Tajima M,
Ideta R,
Nakaya Y,
Arase S,
Kishimoto J.
Source
Department of Dermatology, School of Medicine, University of Tokushima, Tokushima, Japan.
Abstract
Adenosine upregulates the expression of vascular endothelial growth factor and fibroblast growth factor-7 in cultured dermal papilla cells. It has been shown that, in Japanese men, adenosine improves androgenetic alopecia due to the thickening of thin hair due to hair follicle miniaturization. To investigate the efficacy and safety of adenosine treatment to improve hair loss in women, 30 Japanese women with female pattern hair loss were recruited for this double-blind, randomized, placebo-controlled study. Volunteers used either 0.75% adenosine lotion or a placebo lotion topically twice daily for 12 months. Efficacy was evaluated by dermatologists and by investigators and in phototrichograms. As a result, adenosine was significantly superior to the placebo according to assessments by dermatologists and investigators and by self-assessments. Adenosine significantly increased the anagen hair growth rate and the thick hair rate. No side-effects were encountered during the trial. Adenosine improved hair loss in Japanese women by stimulating hair growth and by thickening hair shafts. Adenosine is useful for treating female pattern hair loss in women as well as androgenetic alopecia in men.
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Dermal benefits of topical D-riboseAbstract
Our aging skin undergoes changes with reductions in collagenous and elastic fibers, fibroblasts, mast cells, and macrophages with free radical production, which can result in reduced skin tone and wrinkle formation. Fibroblasts are important for dermal integrity and function with a decrease in function producing less skin tone, thinning, and wrinkle formation. Dermal levels of adenosine triphosphate (ATP) decline with aging, potentially altering dermal function. Supplemental D-ribose, a natural occurring carbohydrate, enhances ATP regeneration. D-ribose-based studies demonstrated benefits in both cell culture fibroblastic activities and a subsequent clinical study in women with decreased skin tone with wrinkles. Supplemental D-ribose may offer this needed cellular benefit.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047922/
Dermal penetration of creatine from a face-care formulation containing creatineJ Cosmet Dermatol. 2011 Dec;10(4):273-81. doi: 10.1111/j.1473-2165.2011.00579.x.
Dermal penetration of creatine from a face-care formulation containing creatine, guarana and glycerol is linked to effective antiwrinkle and antisagging efficacy in male subjects.
Peirano RI,
Achterberg V,
Düsing HJ,
Akhiani M,
Koop U,
Jaspers S,
Krüger A,
Schwengler H,
Hamann T,
Wenck H,
Stäb F,
Gallinat S,
Blatt T.
Source
Department of Skin Biology and Skin Structure, Beiersdorf AG Research and Development, Unnastrasse 48, Hamburg, Germany.
Abstract
BACKGROUND:
The dermal extracellular matrix provides stability and structure to the skin. With increasing age, however, its major component collagen is subject to degeneration, resulting in a gradual decline in skin elasticity and progression of wrinkle formation. Previous studies suggest that the reduction in cellular energy contributes to the diminished synthesis of cutaneous collagen during aging.
AIMS:
To investigate the potential of topically applied creatine to improve the clinical signs of skin aging by stimulating dermal collagen synthesis in vitro and in vivo.
PATIENTS/METHODS:
Penetration experiments were performed with a pig skin ex vivo model. Effects of creatine on dermal collagen gene expression and procollagen synthesis were studied in vitro using cultured fibroblast-populated collagen gels. In a single-center, controlled study, 43 male Caucasians applied a face-care formulation containing creatine, guarana extract, and glycerol to determine its influence on facial topometric features.
RESULTS:
Cultured human dermal fibroblasts supplemented with creatine displayed a stimulation of collagen synthesis relative to untreated control cells both on the gene expression and at the protein level. In skin penetration experiments, topically applied creatine rapidly reached the dermis. In addition, topical in vivo application of a creatine-containing formulation for 6 weeks significantly reduced the sagging cheek intensity in the jowl area as compared to baseline. This result was confirmed by clinical live scoring, which also demonstrated a significant reduction in crow's feet wrinkles and wrinkles under the eyes.
CONCLUSIONS:
In summary, creatine represents a beneficial active ingredient for topical use in the prevention and treatment of human skin aging.
© 2011 Wiley Periodicals, Inc.
Adenosine promotes wound healing and mediates angiogenesis in response to tissue injury via occupancy of A(2A) receptors.
Montesinos MC,
Desai A,
Chen JF,
Yee H,
Schwarzschild MA,
Fink JS,
Cronstein BN.
Source
Department of Medicine, New York University School of Medicine, New York, New York, USA.
Abstract
Recent evidence indicates that topical application of adenosine A(2A) receptor agonists, unlike growth factors, increases the rate at which wounds close in normal animals and promotes wound healing in diabetic animals as well as growth factors, yet neither the specific adenosine receptor involved nor the mechanism(s) by which adenosine receptor occupancy promotes wound healing have been fully established. To determine which adenosine receptor is involved and whether adenosine receptor-mediated stimulation of angiogenesis plays a role in promotion of wound closure we compared the effect of topical application of the adenosine receptor agonist CGS-21680 (2-p-[2-carboxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-adenosine) on wound closure and angiogenesis in adenosine A(2A) receptor knockout mice and their wild-type littermates. There was no change in the rate of wound closure in the A(2A) receptor knockout mice compared to their wild-type littermates although granulation tissue formation was nonhomogeneous and there seemed to be greater inflammation at the base of the wound. Topical application of CGS-21680 increased the rate of wound closure and increased the number of microvessels in the wounds of wild-type mice but did not affect the rate of wound closure in A(2A) receptor knockout mice. Similarly, in a model of internal trauma and repair (murine air pouch model), endogenously produced adenosine released into areas of internal tissue injury stimulates angiogenesis because there was a marked reduction in blood vessels in the walls of healing air pouches of A(2A) receptor knockout mice compared to their wild-type controls. Inflammatory vascular leakage and leukocyte accumulation in the inflamed air pouch were similarly reduced in the A(2A) receptor knockout mice reflecting the reduced vascularity. Thus, targeting the adenosine A(2A) receptor is a novel approach to promoting wound healing and angiogenesis in normal individuals and those suffering from chronic wound
http://www.ncbi.nlm.nih.gov/pubmed/12057906
Adenosine receptors in wound healing, fibrosis and angiogenesis.
Feoktistov I,
Biaggioni I,
Cronstein BN.
Source
Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN 37232-6300, USA.
igor.feoktistov@vanderbilt.edu
Abstract
Wound healing and tissue repair are critical processes, and adenosine, released from injured or ischemic tissues, plays an important role in promoting wound healing and tissue repair. Recent studies in genetically manipulated mice demonstrate that adenosine receptors are required for appropriate granulation tissue formation and in adequate wound healing. A(2A) and A(2B) adenosine receptors stimulate both of the critical functions in granulation tissue formation (i.e., new matrix production and angiogenesis), and the A(1) adenosine receptor (AR) may also contribute to new vessel formation. The effects of adenosine acting on these receptors is both direct and indirect, as AR activation suppresses antiangiogenic factor production by endothelial cells, promotes endothelial cell proliferation, and stimulates angiogenic factor production by endothelial cells and other cells present in the wound. Similarly, adenosine, acting at its receptors, stimulates collagen matrix formation directly. Like many other biological processes, AR-mediated promotion of tissue repair is critical for appropriate wound healing but may also contribute to pathogenic processes. Excessive tissue repair can lead to problems such as scarring and organ fibrosis and adenosine, and its receptors play a role in pathologic fibrosis as well. Here we review the evidence for the involvement of adenosine and its receptors in wound healing, tissue repair and fibrosis.
http://www.ncbi.nlm.nih.gov/pubmed/19639289
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Abstract
Adenosine—a purine nucleoside generated extracellularly from adenine nucleotides released by cells as a result of direct stimulation, hypoxia, trauma, or metabolic stress—is a well-known physiologic and pharmacologic agent. Recent studies demonstrate that adenosine, acting at its receptors, promotes wound healing by stimulating both angiogenesis and matrix production. Subsequently, adenosine and its receptors have also been found to promote fibrosis (excess matrix production) in the skin, lungs, and liver, but to diminish cardiac fibrosis.
A commonly ingested adenosine receptor antagonist, caffeine, blocks the development of hepatic fibrosis, an effect that likely explains the epidemiologic finding that coffee drinking, in a dose-dependent fashion, reduces the likelihood of death from liver disease. Accordingly, adenosine may be a good target for therapies that prevent fibrosis of the lungs, liver, and skin.
http://f1000.com/prime/reports/b/3/21/
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Use of D-ribose, including as a topical vehicle, to promote faster healing, including from surgical procedures
http://www.google.com/patents/US20040127428
