Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging

Park, Gaeun; Baek, Sohee; Kim, Jong‐Eun; Lim, Tae‐Gyu; Lee, Charles C.; Yang, Hee Seok; Kang, Young‐Gyu; Park, Jun Seong; Augustin, Martin; Mrosek, Michael; Lee, Chang Yong; Dong, Zigang; Huber, Robert; Lee, Ki Won

doi:10.1016/j.bcp.2015.08.104

Cited by 47 publications

(38 citation statements)

References 45 publications

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“…UV irradiation may induce abundant secretion of matrix metalloproteinases (MMPs) from fibroblasts and keratinocytes, particularly matrix metalloproteinase-1 (MMP-1), which results in abnormal degradation of the extracellular matrix (1). MMP-1 expression during photo-aging is primarily controlled by the mitogen-activated protein kinase (MAPK) signaling pathway (3). A previous study confirmed that UV-induced reactive oxygen species (ROS) promote MMP-1 expression and induce the occurrence of photo-aging by upregulating phosphorylation levels of the MAPK signaling pathway elements c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 (4).…”

Section: Introductionmentioning

confidence: 99%

MALAT1 participates in ultraviolet B-induced photo-aging via regulation of the ERK/MAPK signaling pathway

Zeng

et al. 2017

Molecular Medicine Reports

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Long non-coding RNA (lncRNA), transcripts of >200 bp in length that do not appear to exhibit any coding capacity, are important in the occurrence and development of cancer, cardiovascular and neurological diseases. However, effects of lncRNAs on photo-aging remain to be elucidated. To explore the potential effects of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on photo-aging in fibroblasts, MALAT1 expression was silenced in fibroblasts using small interference RNA. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to examine MALAT1 expression in normal and silenced fibroblasts following irradiation with 60 mJ/cm2 ultraviolet B (UVB) and an ELISA assay was used to identify matrix metalloproteinase-1 (MMP-1) content in the cellular supernatant. A β-galactosidase kit was applied to measure the number of senescent cells and a western blot assay was used to detect extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 phosphorylation levels. RT-qPCR was additionally used to detect changes in MALAT1 expression following suppression of UVB-induced reactive oxygen species (ROS) generation with N-acetyl-L-cysteine (NAC). Fibroblasts irradiated with 60 mJ/cm2 UVB demonstrated increased MALAT1 expression, MMP-1 secretory volume and number of senescent cells, and greater levels of ERK, p38 and JNK phosphorylation. Following silencing of MALAT1 expression in photo-aged fibroblasts, decreases were observed in MMP-1 secretory volume, number of senescent cells and phosphorylation levels of ERK. NAC reduced ROS content, however, it did not affect MALAT1 expression. Therefore, it was concluded that MALAT1 may participate in UVB-induced photo-aging via regulation of the ERK/mitogen-activated protein kinase signaling pathway and UVB-induced MALAT1 expression is independent of ROS generation.

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Section: Introductionmentioning

confidence: 99%

MALAT1 participates in ultraviolet B-induced photo-aging via regulation of the ERK/MAPK signaling pathway

Zeng

et al. 2017

Molecular Medicine Reports

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“…9) In addition, coumestrol shows anti-aging effects on skin and inhibits UVB-induced matrix metallopeptidase (MMP)-1 expression by suppressing the kinase activity of fms-related tyrosine kinase 3 (FLT3). 10) However, no studies have investigated the effects of coumestrol on melanogenesis or skin hyperpigmentation. In this study, we provide the first report of the anti-melanogenic actions of coumestrol, demonstrating that the effects of coumestrol are mediated by down-regulation of the protein level of tyrosinase, a key melanogenic enzyme.…”

mentioning

confidence: 99%

Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase

Hwang

Park

et al. 2017

Biological & Pharmaceutical Bulletin

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Pigmentation reflects skin darkening caused by melanin production, but excessive melanin synthesis may cause problems, such as melasma, solar lentigo, dark spots, and freckles. Considerable effort has been devoted to alleviating these undesired symptoms through the development of safe and effective depigmenting agents. Coumestrol, a plant-derived natural isoflavone with an estrogen-like structure and actions, is known to have anti-aging ability, but its potential depigmenting efficacy has not been evaluated. In the present study, we investigated the effects of coumestrol on melanin synthesis in normal melan-a murine melanocytes. Coumestrol significantly reduced melanin synthesis in a concentration-dependent manner up to a concentration of 25 µM without causing cytotoxicity. It also brightened tissue in an artificial skin model (MelanoDerm) that incorporates both human keratinocytes and melanocytes. Interestingly, although coumestrol did not inhibit tyrosinase activity or transcript level in melan-a cells, it clearly decreased the expression level of tyrosinase protein at a concentration of 25 µM. This coumestrol-induced reduction in tyrosinase protein levels was prevented by pretreatment with the proteasome inhibitor MG-132 or the lysosomal proteolysis inhibitor chloroquine. Collectively, our findings indicate that coumestrol exerts an inhibitory effect on melanin synthesis in melan-a cells, at least in part, through degradation of tyrosinase. These findings suggest that coumestrol is a good candidate for use in depigmentary reagents from a cosmetic and clinical perspective.

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“…In a number of recent studies, it has been shown that each isoflavone elicits additional health benefits through specific molecular targets. Of particular note, genistein is regarded as a tyrosine kinase inhibitor [35], while other isoflavones have been shown to interact with molecular targets relevant to human health [36]. Studies have also shown that isoflavones are effective only if there is a specific strain of microbiota in the body, which can convert daidzein to equol.…”

Section: Soy Isoflavonesmentioning

confidence: 99%

“…These isoflavones are present in very low concentrations in soybeans, although they may increase during fermentation. Recently, through bioconversion using enzymes or microorganisms for functional food or cosmetic applications [36]. 6,7,4'-trihydroxyisoflavone (THIF), a metabolite of daidzein, exhibits anti-wrinkle formation properties via direct suppression of PKCα kinase activity [41].…”

Section: Soy Isoflavonesmentioning

confidence: 99%

Review of Soybean Phytochemicals and Their Bioactive Properties Relevant for Skin Health

Kim¹,

Kang²,

Park³

et al. 2017

JFNR

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Numerous studies have investigated the bioactive properties of compounds present in soybean (Glycine max) that may have beneficial effects on the health of human skin. Several such compounds have already been introduced into commercial cosmetic products to promote functional properties such as skin whitening, anti-wrinkle activity and skin hydration. However, a significantly greater understanding of the application of soybean ingredients in these types of products is needed before optimal benefits can be realized. In this review, we aim to summarize some of the biological properties of soybean constituents and the underlying mechanisms of action responsible for beneficial effects in skin. In addition, we will discuss future directions for studies that may help to expand the applications for soybean compounds.

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Flt3 is a target of coumestrol in protecting against UVB-induced skin photoaging

Cited by 47 publications

References 45 publications

MALAT1 participates in ultraviolet B-induced photo-aging via regulation of the ERK/MAPK signaling pathway

MALAT1 participates in ultraviolet B-induced photo-aging via regulation of the ERK/MAPK signaling pathway

Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase

Review of Soybean Phytochemicals and Their Bioactive Properties Relevant for Skin Health

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