Human hair follicle pigmentary unit as a direct target for modulators of melanogenesis, as studied by [<sup>14</sup>C]‐2‐Thiouracil incorporation

Michelet, Jean‐François; Gautier, Brigitte; Gaillard, O; Bernard, Bruno; Benech, Florence

doi:10.1111/j.1600-0625.2008.00804.x

Cited by 3 publications

(3 citation statements)

References 17 publications

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“…The R151C+/− cells also responded in a similar fashion to WT MC1R strains, while the R160W+/− and D294H+/− cells reacted weakly to NDP‐MSH, but were still able to respond fully to forskolin, showing cAMP pathways were not affected. This is in agreement with earlier studies that also noted variable heterozygote effects (14,15).…”

Section: Resultssupporting

confidence: 94%

Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes

Ainger

Wong

Roberts

et al. 2011

Experimental Dermatology

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epidermal components. Immunohistochemically, the regenerated hairs were positive for loricrin, filaggrin, keratin 10, p63 and Ki67 in a similar pattern to normal skin . There remained a possibility that the difference in media between the two-dimensional and three-dimensional culture accounted for the difference in the hair-inducing capacity of transplanted cells. However, in our preliminary experiments (n = 12), we could not observe hair regeneration in the co-transplantation of epidermal cells and twodimensionally cultured dermal cells maintained in the medium used for the three-dimensional culture condition (DMEM: F12 + B27 + EGF + bFGF).Our data described previously raise a possibility that sphere formation may be sufficient to give mesenchymal cells hair-inducing capacity regardless of the cell identity as dermal cells. To test this, we selected lungs as the origin of mesenchymal cells outside the dermis. Immunohistochemistry showed that some cells stained positive for both Sca-1 and nestin in adult lungs ( Fig. 2a-d). We cultured dissociated lung cells in two-dimensional culture condition and thereafter transferred them into the sphere-forming condition. They formed spheroids (Fig. 2e) in which some cells expressed Sca-1, nestin and fibronectin ( Fig. 2f-i). Each cell attached directly to one another by adherens junctions (Fig. 2j). Of the genes for Wnt ligand members, wnt5a and wnt5b, b-catenin and lef-1 were significantly upregulated during cultivation in the sphere-forming condition ( Fig. 2k-n). Co-transplantation of epidermal cells and sphere-forming lung cells regenerated black hairs in the transplanted area (9 ⁄ 13) ( Fig. 2o, q). Occasionally, epidermal cysts, presumably formed by transplanted epidermal cells that failed to participate in hair follicles, were observed (Fig. 2q). On the contrary, co-transplantation of epidermal cells and two-dimensionally lung cells did not regenerate hairs (0 ⁄ 9) (Fig. 2p, r). We traced the transplanted lung cells derived from CAG-EGFP mice and found that GFP + cells are localized in the dermal papilla and in the sub-epidermal lesion (Fig. 2s, t). The regenerated hairs showed normal expression pattern for loricrin, filaggrin, keratin 10, p63 and Ki67 (Fig. S3k-t). ConclusionIn summary, mesenchymal cells obtain hair-inducing capacity through sphere formation, even if the cell does not originally possess dermal cell identity. Our data provide a new methodology to successfully expand the hair follicle niche cells for regenerative medicine of hair follicles. Two-dimensionally expanded mesenchymal cells that have once lost their potential as hair-inducing niche cells can recover hair-inducing capacity in sphere-forming culture. AcknowledgementsThis work was supported by Grants-in-Aid for Specially Promoted Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Conflict of interestsThe authors state no conflict of interest. Supporting InformationAdditional Supporting Information may be found in the online version of this article: Fig...

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Section: Resultssupporting

confidence: 94%

Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes

Ainger

Wong

Roberts

et al. 2011

Experimental Dermatology

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“…Skin: It has been reported that forskolin after a relatively long lag period, induced the production of melatonin in cultured Syrian hamster pineal glands [118]. Forskolin was found to cause a significant increase in human hair follicle melanogenic activity and consequently a significant increase in pigmented hair follicles [119], and to stimulate the growth of hair follicular keratinocytes and melanogenesis in vitro [120,121]. In addition, it has been demonstrated that compositions containing solubilized 2 % w/w of forskolin and 5% freeze-dried liquid endosperm of Cocos nucifera or 1 % forskolin and 1 % 9,10-dimethoxy-2-mesitylimino-3methyl-2,3,6,7-tetrahydo-4H-pyrimido[6,1-a]isoquinolin-4-one hydrochloride were able to promote hair growth in animal models [122,123].…”

Section: Forskolinmentioning

confidence: 99%

Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Alasbahi

Melzig²

2010

Planta Med

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Pharmacology ! Plectranthus barbatusStudies on several extracts with various polarities obtained from different parts of P. barbatus revealed a number of pharmacological properties that may justify most of the traditional uses of P. barbatus, for example, organic extracts were reported to possess anti-inflammatory, antimicrobial [1, 2], antioxidant [3], cytotoxic [4], hypotensive [5,6], spasmolytic [7], hepatoprotective [8] and antifeedant [9] activities as well as activity against Ehrlichʼs ascites tumor in mice [10]. An alcoholic extract of the P. barbatus roots was shown to exhibit marked inhibitory action against Escherichia coli toxin-induced secretory response in rabbits and guinea pig ileal loops [11]. It has been shown that a hydroalcoholic extract of P. barbatus (880 mg/kg/day) exerted a variety of toxic effects on the different periods of pregnancy in rats; for example, in the period before embryo implantation, it caused a delay in fetal development and anti-implantation and, after embryo implantation, a delay in the development associated with maternal toxicity [12]. The water extract of P. barbatus leaves was found to exert hypoglycemic, hypotensive and antispasmodic activities [13]. It has been demonstrated that the water extract (WE) of the stems and leaves, at a dose of 1 g/kg p. o., shortened the sleeping time induced by pentobarbital by 37 %, and at a dose of 2 g/kg p. o. enhanced the intestinal transit of charcoal by 30% in mice. The WE (2 g/kg/intraduodenal) also reduced the gastric secretions (3.9 ± 1.0 to 0.5 ± 0.2 mL/4 h), and total acid secretion (34.4 ± 11.0 to 2.7 ± 0.5 mEq/L) and raised gastric pH (2.2 ± 0.3 to 6.5 ± 0.8) in rats. The treatment with WE (2 g/ kg p. o.) was also found to protect against lesions induced by ethanol or cold-restraint stress, in pylorus-ligated rats [14]. Similar results were obtained by Schultz et al. [15] who reported that the WE of the leaves (0.5-0.1 g/kg) injected into the duodenal lumen decreased the volume (62 and 76 %) and total acidity (23 and 50%) of gastric Abstract ! Plectranthus barbatus Andr. is one of the most important species of the genus Plectranthus L′ Herit. (Lamiaceae), with a wide variety of traditional medicinal uses in Hindu and Ayurvedic traditional medicine as well as in the folk medicine of Brazil, tropical Africa and China. The plant has therefore been an attractive target for intensive chemical and pharmacological studies up to now. This review presents data about the phytochemistry, ethnobotanical uses and pharmacology of Plectranthus barbatus as well as the pharmacology of its constituents. In addition to essential oil, abietane diterpenoids and 8,13-epoxy-labd-14-en-11-one diterpenoids are the main constituents found in Plectranthus barbatus. The major ethnobotanical uses are for intestinal disturbance and liver fatigue, respiratory disorders, heart diseases and certain nervous system disorders. Forskolin as one of the major constituents with its unique adenylyl cyclase activation that underlies the wide range of pharmacologic...

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“…De Vries and co-workers proposed using a topical cAMP approach to regulate beta-adrenergic response in psoriasis patients [71]. Interestingly, cAMP stimulation has also been studied as an activator of hair follicle activity and has been considered as a therapy for age-related hair loss [72, 73]. We and others have been interested in the UV-protective consequences of topical cAMP induction to promote melanin protection from UV-mediated DNA damage [68] and to enhance levels and/or activity of key DNA repair and antioxidant enzymes [74].…”

Section: Forskolin Rescues Camp Deficient Signalingmentioning

confidence: 99%

Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

2014

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Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of “realized” solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations.

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Human hair follicle pigmentary unit as a direct target for modulators of melanogenesis, as studied by [¹⁴C]‐2‐Thiouracil incorporation

Abstract: The purpose of this study was to evaluate human hair follicle melanogenic activity using the

Cited by 3 publications

References 17 publications

Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes

Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes

Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

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Human hair follicle pigmentary unit as a direct target for modulators of melanogenesis, as studied by [14C]‐2‐Thiouracil incorporation

Abstract: The purpose of this study was to evaluate human hair follicle melanogenic activity using the

Cited by 3 publications

References 17 publications

Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes

Effect of MC1R variant allele status on MSH-ligand induction of dopachrome tautomerase in melanocytes co-cultured with keratinocytes

Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Ultraviolet Radiation, Aging and the Skin: Prevention of Damage by Topical cAMP Manipulation

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Human hair follicle pigmentary unit as a direct target for modulators of melanogenesis, as studied by [¹⁴C]‐2‐Thiouracil incorporation