Abstract:
BACKGROUND:As interest in skin beauty increases, the development of new skin whitening agents has attracted substantial attention; however, the action mechanism of the agents developed so far remains largely unknown. Tranexamic acid (TXA) is commonly being used to reduce melanin synthesis in patients with melasma and also used as a raw material for functional whitening cosmetics, although its action mechanism is poorly understood. Autophagy has been well known to be essential for tissue homeostasis, adaptation to starvation, and removal of dysfunctional organelles or pathogens. Recent studies have shown that autophagy regulators might have prominent roles in the initial formation stage of the melanosome, a lysosome-related organelle synthesizing melanin pigments. However, there is still no direct evidence showing a relationship between the activation of the autophagy system and the melanogenesis. OBJECTIVE:To investigate whether TXA can inhibit melanogenesis through the activation of autophagy in a melanoma cell line. METHODS:B16-F1 melanoma cells were treated with TXA and the levels of autophagy- and melanogenesis-related proteins were determined by Western blottings. The direct effect of TXA-mediated autophagy activation on melanin production was further evaluated by transfecting the cells with 60 pmols of small interfering RNAs (siRNAs)-targeting the mechanistic target of rapamycin (mTOR) and the autophagy-related protein 5 (Atg5). RESULTS:The results of Western blottings showed that TXA enhanced the production of autophagy-related proteins such as mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK)1/2, Beclin-1, Atg12, and light chain 3 (LC3) I-II, whereas it decreased the synthesis of the mTOR complex. Confocal microscopy clearly showed that TXA treatment resulted in the formation of autophagosomes in B16-F1 cells, as revealed by immunostaining with an anti-LC3 antibody. The production of melanogenesis-associated proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 1 and 2 (TRP1/2), were clearly downregulated by the treatments with TXA. These results suggest that TXA can mediate a decrease in melanin synthesis by alleviating the production of tyrosinase and TRP1/2, along with lowered MITF protein levels. Furthermore, after treatment with TXA, siRNAs- targeting to mTOR and Atg5 increased melanin synthesis by 20% and 40%, respectively, compared to that in non-transfected cells, in a dose-dependent manner. These results further confirmed that TXA can inhibit melanogenesis by activating the autophagy system. CONCLUSION:Collectively, the results demonstrate that TXA can reduce melanin synthesis in melanoma B16-F1 cells by activating the ERK signaling pathway and the autophagy system.
journal_name
J Dermatol Scijournal_title
Journal of dermatological scienceauthors
Cho YH,Park JE,Lim DS,Lee JSdoi
10.1016/j.jdermsci.2017.05.019subject
Has Abstractpub_date
2017-10-01 00:00:00pages
96-102issue
1eissn
0923-1811issn
1873-569Xpii
S0923-1811(17)30540-6journal_volume
88pub_type
杂志文章abstract:BACKGROUND:The tetracycline (Tet) responsive system is a valuable tool that is routinely used in a wide variety of mammalian cells for regulatable expression of gene products. However, technical difficulties such as harsh selection conditions and extensive screening processes to identify suitably responsive clones limi...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2007.09.003
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Extramammary Paget's disease (EMPD) is a rare skin cancer that frequently occurs in the anogenital region in the elderly. Prognosis in patients with metastatic EMPD is poor as EMPD treatment has advanced little in recent years, primarily because no EMPD cell line has been established. OBJECTIVE:We aimed to ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2020.07.006
更新日期:2020-09-01 00:00:00
abstract::Systemic sclerosis (SSc) is a connective tissue disease with unknown etiology characterized by excessive deposition of collagen in the skin as well as various internal organs. One of the characteristic histological features is the presence of infiltrating mononuclear cells in the dermis in its early stage. As well as ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(00)00169-9
更新日期:2001-06-01 00:00:00
abstract::DS-Nh (DS Nh/+) mice spontaneously develop dermatitis when they are housed in a conventional environment. In this study, we analyzed the clinical and histopathological features of dermatitis in DS-Nh mice, which is characterized by erythema, edema, and erosion on the face, neck, chest and flexor surfaces of their fore...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(02)00070-1
更新日期:2002-11-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. Enhanced expression of matrix metalloproteinase-2 (MMP-2) has been demonstrated in dermatofibroma (DF) and malignant fibrous histiocytoma (MFH). MMP-2 has been shown to be activated by membrane-type MMPs (MT-MMPs). To study the r...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(01)00159-1
更新日期:2002-02-01 00:00:00
abstract::Crude enzyme solutions of prolidase were extracted from cultured human skin fibroblasts derived from control and prolidase-deficient sisters. Two forms of prolidases (prolidase-I and II) were partially purified by high performance liquid chromatography equipped with an ion exchange column. On gel filtration, the relat...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(90)90588-5
更新日期:1990-09-01 00:00:00
abstract::Survival and extracellular matrix gene expression were studied by viable cell count assay and Northern transfer analysis to compare the sensitivity of normal skin and keloid fibroblasts towards x-irradiation. As the dosage of radiation increased, the numbers of viable cells in irradiated groups were remarkably decreas...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(94)90318-2
更新日期:1994-08-01 00:00:00
abstract::Propionibacterium acnes (P. acnes) causes an inflammatory acne that is characterized by massive neutrophilic infiltration. IL-8 is thought to play an important role in the pathophysiology of P. acnes, although the mechanisms by which P. acnes up-regulates the release of IL-8, a neutrophilic chemokine, from target cell...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(02)00013-0
更新日期:2002-08-01 00:00:00
abstract::Stratum corneum samples obtained from 46 members in three generations of seven families were analyzed for keratin pattern by gel electrophoresis. All these samples of apparently normal upper arm skin expressed the 55 kDa, 56.5 kDa, and 65 kDa keratin proteins; while only 28%, 20% and 48% of the samples expressed the 5...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(90)90118-w
更新日期:1990-07-01 00:00:00
abstract::Genetic syndromes with skin fragility represent a heterogeneous group of very rare disorders caused by mutations in genes encoding proteins or protein subunits important for the mechanical resistance of keratinocytes and for cell-cell or cell-extracellular matrix adhesion. The common symptoms are skin blistering or pe...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2006.08.003
更新日期:2006-12-01 00:00:00
abstract::We have studied the distribution of SH groups and SS linkages in solar elastosis, in comparison with that in aged and juvenile sun-unexposed skin, using N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) stain. In heavy solar elastosis we found increased fluorescence for SS bonds in the upper and middle reticu...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(94)90017-5
更新日期:1994-02-01 00:00:00
abstract:BACKGROUND:Due to their immunosuppressive therapy, organtransplant recipients (OTRs) exhibit a high incidence for the development of cutaneous squamous cell carcinoma (cSCC). Randomized studies of kidney-transplanted patients indicate a significant lower susceptibility for cSCC among patients receiving the mTOR-inhibit...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2018.08.013
更新日期:2018-11-01 00:00:00
abstract::Hamster flank organs are useful for studying androgen-dependent growth of hair follicles and sebaceous glands. A cDNA clone (FAR-17a) was isolated from the hamster flank organ, whose expression was highly sensitive to androgen. The mRNA level of this gene was reduced after castration but reappeared after testosterone ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(97)00597-5
更新日期:1997-05-01 00:00:00
abstract::Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are considered part of a spectrum of adverse cutaneous drug reactions showing severe and extensive skin detachment. TEN and SJS are morphologically characterized by active apoptotic keratinocyte cell death that results in the separation of the epiderm...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/j.jdermsci.2008.06.003
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:The capacity of photosensitizing chemicals with ultraviolet A light (UVA) to induce apoptosis is one of the methods to assess their phototoxic and potentially photoallergic properties, since apoptotic cells may be easily presented by antigen-presenting cells. OBJECTIVES:We examined the photoaggravated abili...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2006.10.010
更新日期:2007-02-01 00:00:00
abstract::A simple method is described for the procurement of human blood eosinophil phenotypes by combining an anti-CD16 monoclonal antibody, immunobeads, and a non-toxic and non-ionic density gradient medium, Nycodenz. The purification depends on the removal of mononuclear cells using a 1.076/1.102 g/ml Nycodenz density gradi...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(95)00394-8
更新日期:1995-09-01 00:00:00
abstract:BACKGROUND:Vitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood. OBJECTIVE:The aim of the current study was to investigate whether vitiligo and halo nevus...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2017.03.008
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:Transforming growth factor beta 1 (TGFβ) is known to be a regulator of autoimmunity. Loss of TGFβ leads to severe multi-organ autoimmunity in mice. In skin, role of TGFβ in suppressing autoimmunity is unclear. OBJECTIVE:Determine whether Keratinocyte (KC)-derived TGFβ is required for skin immune homeostasis...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2019.04.008
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Optical coherence tomography (OCT) is a promising non-invasive imaging technique that has not systematically been studied in skin cancer such as basal cell carcinoma (BCC). OBJECTIVE:We aimed, first, to describe the in vivo histologic features of BCC by using OCT, and second, to find out whether it is possi...
journal_title:Journal of dermatological science
pub_type: 临床试验,杂志文章
doi:10.1016/j.jdermsci.2006.11.012
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:The molecular pathogenesis of mycosis fungoides (MF) is currently poorly understood. The chemokine receptor CCR7 has been demonstrated to be involved in the development and progression of certain cancers, but its role in MF has rarely been investigated. OBJECTIVES:We seek to determine whether CCR7 is expres...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2013.12.003
更新日期:2014-04-01 00:00:00
abstract::Thiols are of great importance for the regulation of many cellular functions including metabolism, transport and cell protection. In this study the usefulness of L-cysteine methyl and octyl esters, of N,S-diacetyl-L-cysteine methyl ester and glutathione isopropyl ester as cellular cysteine and GSH delivery systems was...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(90)90008-2
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND:Tyrosinase, the rate-limiting enzyme required for melanin production, has been targeted to develop active brightening/lightening materials for skin products. Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibitin...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2014.07.001
更新日期:2014-10-01 00:00:00
abstract::We previously reported a simple and easy-to-use device, Scratch Monitor for evaluation of nocturnal scratching. In the present study, the effect of an antihistamine (azelastine hydrochloride) on atopic dermatitis was investigated using this device. In 40 patients with atopic dermatitis, nocturnal scratching was measur...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(99)00048-1
更新日期:1999-12-01 00:00:00
abstract:BACKGROUND:Skin derived precursors (SKP) comprise a subset of specialized dermal cells that can be distinguished from fibroblast by their capacity for spheroidal growth. Recent investigations have shown that hair follicles constitute a niche for this cell type, but their localization and their definite function in non-...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2012.10.007
更新日期:2013-02-01 00:00:00
abstract::The vasculature in adult skin remains normally quiescent, due to the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli. However, skin retains the capacity for brisk initiation of angiogenesis, the growth of new blood vessels from preexisting vessels, during tissue repair and in numerous ...
journal_title:Journal of dermatological science
pub_type: 杂志文章,评审
doi:10.1016/s0923-1811(00)00145-6
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Pachydermoperiostosis (PDP) is a rare genetic disorder characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and finger clubbing. Recently, a homozygous mutation in the gene HPGD, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), was found to be assoc...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2012.07.008
更新日期:2012-10-01 00:00:00
abstract::Keratinocyte growth factor (KGF) is a stromally derived paracrine mitogen that belongs to the fibroblast growth factor (FGF) family. It is secreted by dermal fibroblasts and specifically promotes keratinocyte proliferation. We have recently shown that epidermal growth factor (EGF) and transforming growth factor beta (...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/0923-1811(94)00350-n
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND:Psoriasis is a chronic inflammatory disease characterized by demarcated, raised, and scaling skin lesions. It often serves as a model for immune-mediated disorders. Gene expression profiling of affected skin has allowed insights into psoriasis pathogenesis. However, the mechanisms leading to specific mRNA ex...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2019.11.003
更新日期:2020-01-01 00:00:00
abstract::Quinolone antibacterial agents, known to elicit photosensitive dermatitis as an adverse effect, have both phototoxicity and photoallergenicity. The latter potency is mainly derived from their photohaptenic moiety; quinolones covalently bind to protein and cells upon exposure to ultraviolet A (UVA) light. Our previous ...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/s0923-1811(99)00011-0
更新日期:1999-09-01 00:00:00
abstract:BACKGROUND:Canine atopic dermatitis (cAD) is a common condition in dogs that may be a naturally occurring model for human atopic dermatitis (hAD). Despite this, comparative research is limited, particularly into the genetic background of cAD. OBJECTIVES:1. Measure candidate gene expression in cAD skin using quantitati...
journal_title:Journal of dermatological science
pub_type: 杂志文章
doi:10.1016/j.jdermsci.2009.03.005
更新日期:2009-07-01 00:00:00