CCN1/Cyr61 Stimulates Melanogenesis through Integrin α6β1, p38 MAPK, and ERK1/2 Signaling Pathways in Human Epidermal Melanocytes

Xu, Zhongyi; Chen, Li; Jiang, Min; Wang, Qianqian; Zhang, Chengfeng; Xiang, Leihong

doi:10.1016/j.jid.2018.02.029

Cited by 28 publications

(15 citation statements)

References 55 publications

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“…Jun et al reported that in the course of cutaneous wound repair, the highly expressed CCN1 in granulation tissue would promote the senescence of fibroblasts and regulate the expressions of anti‐fibrotic genes to suppress the fibrosis . Xu et al found that ultraviolet B irradiation could stimulate the secretion of CCN1 in normal human dermal fibroblasts . Our results revealed that both HA ceramics could also stimulate the CCNI secretion to induce the senescence of HSF cells, as was influenced by the surface microstructure of the ceramics.…”

Section: Discussionsupporting

confidence: 51%

Effect of surface microstructure on the anti‐fibrosis/adhesion of hydroxyapatite ceramics in spinal repair of rabbits

Liú

Zhou

et al. 2019

J Biomed Mater Res

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Epidural adhesion is a great clinical challenge after laminectomy. In the present study, two types of hydroxyapatite (HA) laminas with distinct surface microstructures were prepared by cold isostatic pressing (CIP) and slip casting (SC) techniques, and investigated to their anti‐fibrosis/adhesion effects by in vitro and in vivo evaluations. In contrast with the dense HA‐CIP, HA‐SC had a large number of micropores on the surface. After cultured on both HA ceramics, human skin fibroblasts presented the obvious senescent feature, and CCN1 gene expression was significantly up‐regulated. HA‐SC induced higher CCN1 gene expression than HA‐CIP. After used for closing the lost vertebral after laminectomy in rabbits, both HA laminas promoted the recovery of the bony structure as well as prevented the hyperplastic fibrous tissue from penetration into the spinal canal area and inhibited the formation of scar‐like tissue in laminectomy sites to some extent. Besides, thinner layer of fibrous tissue and smaller gap between the implant surface and paravertebral muscles were found in HA‐CIP than HA‐SC. Therefore, HA ceramics could have good anti‐fibrosis/adhesion effect when used in spinal repair, and the dense HA‐CIP could be an ideal choice. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2629–2637, 2019.

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Section: Discussionsupporting

confidence: 51%

Effect of surface microstructure on the anti‐fibrosis/adhesion of hydroxyapatite ceramics in spinal repair of rabbits

Liú

Zhou

et al. 2019

J Biomed Mater Res

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“…These results implicate neuregulin-1 in determining constitutive pigmentation, and suggest that it contributes to eumelanin synthesis, which is abundant in dark skin. Another melanogenic factor derived from fibroblasts is CCN1/Cyr61, an extracellular matrix (ECM) protein that was recently reported to increase melanogenesis via binding to integrin α6β1 and activating the MAP kinases p38 and ERK1/2 [ 106 ]. Secretion of CCN1/Cyr61 is enhanced following UV exposure, suggesting that this factor participates in the tanning response of melanocytes to UV.…”

Section: Paracrine Factors As Regulators Of Melanogenesis and The mentioning

confidence: 99%

MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair

Swope

Abdel‐Malek

2018

IJMS

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Melanin, the pigment produced by specialized cells, melanocytes, is responsible for skin and hair color. Skin pigmentation is an important protective mechanism against the DNA damaging and mutagenic effects of solar ultraviolet radiation (UV). It is acknowledged that exposure to UV is the main etiological environmental factor for all forms of skin cancer, including melanoma. DNA repair capacity is another major factor that determines the risk for skin cancer. Human melanocytes synthesize eumelanin, the dark brown form of melanin, as well as pheomelanin, which is reddish-yellow in color. The relative rates of eumelanin and pheomelanin synthesis by melanocytes determine skin color and the sensitivity of skin to the drastic effects of solar UV. Understanding the complex regulation of melanocyte function and how it responds to solar UV has a huge impact on developing novel photoprotective strategies to prevent skin cancer, particularly melanoma, the most fatal form, which originates from melanocytes. This review provides an overview of the known differences in the photoprotective effects of eumelanin versus pheomelanin, how these two forms of melanin are regulated genetically and biochemically, and their impact on the DNA damaging effects of UV exposure. Additionally, this review briefly discusses the role of paracrine factors, focusing on α-melanocortin (α-melanocyte stimulating hormone; α-MSH), in regulating melanogenesis and the response of melanocytes to UV, and describes a chemoprevention strategy based on targeting the melanocortin 1 receptor (MC1R) by analogs of its physiological agonist α-MSH.

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“…The reductions in Netrin‐1 and FGF5 may also contribute to decreased expression of age spots as they decrease melanocyte migration . As we observed a decreased age spot expression clinically following the HSA treatment these changes in vitro must override any positive effects on melanocytes induced by Cyr61 and DKK .…”

Section: Discussionmentioning

confidence: 61%

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

Schütz

Rawlings²,

Wandeler

et al. 2019

Intern J of Cosmetic Sci

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IntroductionWe report on the preparation and efficacy of 10‐hydroxystearic acid (HSA) that improves facial age spots and conspicuous pores.MethodsThe hydration of oleic acid into HSA was catalyzed by the oleate hydratase from Escherichia coli. Following treatment with HSA, collagen type I and type III was assessed in primary human dermal fibroblasts together with collagen type III, p53 protein levels and sunburn cells (SBC) after UVB irradiation (1 J cm−2) by immunohistochemistry on human ex vivo skin. UVB‐induced expression of matrix metalloprotease‐1 (MMP‐1) was determined from full thickness skin by RT‐qPCR. Modification of the fibroblast secretome by HSA was studied by mass‐spectrometry‐based proteomics. In a full‐face, double blind, vehicle‐controlled trial HSA was assessed for its effects on conspicuous facial pore size and degree of pigmentation of age spots in Caucasian women over an 8‐week period.ResultsHSA was obtained in enantiomeric pure, high yield (≥80%). Collagen type I and type III levels were dose‐dependently increased (96% and 244%; P < 0.01) in vitro and collagen type III in ex vivo skin by +57% (P < 0.01) by HSA. HSA also inhibited UVB‐induced MMP‐1 gene expression (83%; P < 0.01) and mitigated SBC induction (−34% vs. vehicle control) and reduced significantly UV‐induced p53 up‐regulation (−46% vs. vehicle control; P < 0.01) in irradiated skin. HSA modified the fibroblast secretome with significant increases in proteins associated with the WNT pathway that could reduce melanogenesis and proteins that could modify dermal fibroblast activity and keratinocyte differentiation to account for the alleviation of conspicuous pores. Docking studies in silico and EC50 determination in reporter gene assays (EC50 5.5 × 10−6 M) identified HSA as a peroxisomal proliferator activated receptor‐α (PPARα) agonist. Clinically, HSA showed a statistically significant decrease of surface and volume of skin pores (P < 0.05) after 8 weeks of application and age spots became significantly less pigmented than the surrounding skin (contrast, P < 0.05) after 4 weeks.ConclusionHSA acts as a PPARα agonist to reduce the signs of age spots and conspicuous pores by significantly modulating the expression of p53, SBC, MMP‐1 and collagen together with major changes in secreted proteins that modify keratinocyte, melanocyte and fibroblast cell behavior.

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CCN1/Cyr61 Stimulates Melanogenesis through Integrin α6β1, p38 MAPK, and ERK1/2 Signaling Pathways in Human Epidermal Melanocytes

Cited by 28 publications

References 55 publications

Effect of surface microstructure on the anti‐fibrosis/adhesion of hydroxyapatite ceramics in spinal repair of rabbits

Effect of surface microstructure on the anti‐fibrosis/adhesion of hydroxyapatite ceramics in spinal repair of rabbits

MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair

Bio‐derived hydroxystearic acid ameliorates skin age spots and conspicuous pores

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