MITF-M regulates melanogenesis in mouse melanocytes

Chen, Tianzhi; Zhao, Bingling; Liu, Yu; Wang, Ruiwei; Yang, Yujing; Yang, Linpei; Dong, Chunhong

doi:10.1016/j.jdermsci.2018.02.008

Cited by 37 publications

(29 citation statements)

References 56 publications

(57 reference statements)

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“…Our findings were able to correlate the successful inhibition of cellular tyrosinase activity with the reduction of cellular melanin content. At transcriptional level, our findings showed that both FLA and FLB significantly suppressed the melanogenic master regulator of Mitf gene expression which in turn suggesting the down-regulation of other melanogenic-related genes including Tyr, Trp-1 and Trp-2 [55]. The successful suppression of Mitf determines the effectiveness of FLA and FLB as potent depigmenting agents since Mitf is essential in melanin-bearing pigment cells across species and tissue types [55,56].…”

Section: Discussionmentioning

confidence: 73%

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)

et al. 2020

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Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.

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Section: Discussionmentioning

confidence: 73%

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)

et al. 2020

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“…Akt, protein kinase B; CREB, CRE-binding protein; ERK, extracellular signaleregulated kinase; GAPDH, glucose-6-phosphate dehydrogenase; JNK, c-Jun N-terminal kinase; MITF, microphthalmiaassociated transcription factor; NC, negative control; p-Akt, phosphorylated protein kinase B; p-CREB, phosphorylated CRE-binding protein; p-ERK, phosphorylated extracellular signaleregulated kinase; p-JNK, phosphorylated c-Jun N-terminal kinase; p-PKA, phosphorylated protein kinase A; p-STAT, phosphorylated STAT; PIG1, human immortalized melanocytes; PKA, protein kinase A; qRT-PCR, quantitative real-time reverse transcriptaseePCR; SEM, standard error of the mean. (Konar et al, 2018;Park et al, 2018), MAPK (Daniel et al, 2018;Fujimura and Usuki, 2018;, Ca 2þ / CaMK (Chen et al, 2018b;Liu et al, 2018), STAT (Deng et al, 2018), and PI3K/Akt (Daniel et al, 2018;Nishina et al, 2018). In this study, we investigated the possible mechanism of UCA1 regulation of CREB through signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Melanogenesis is regulated by a series of transcription factors, among which microphthalmia-associated transcription factor (MITF) plays an important role (Chen et al, 2018b;Ishii et al, 2017). MITF promotes melanogenesis by inducing melanogenesis-related genes, such as TYR, TYRP1, TYRP2, and RAB27A (Alves et al, 2017;Sultana et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The Long Noncoding RNA UCA1 Negatively Regulates Melanogenesis in Melanocytes

Pei

Chen

et al. 2020

Journal of Investigative Dermatology

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The long noncoding RNA UCA1 was first discovered in bladder cancer and is known to regulate the proliferation and migration of melanoma. However, its role in melanogenesis is unclear. In this study, we aimed to explore the role and mechanism of UCA1 in melanogenesis. Our findings showed that the expression of UCA1 was negatively correlated with melanin content in melanocytes and pigmented nevus. Overexpression of UCA1 in melanocytes decreased melanin content and the expression of melanogenesis-related genes, whereas knockdown of UCA1 in melanocytes had the opposite effect. High-throughput sequencing revealed that microphthalmia-associated transcription factor (MITF), an important transcription factor affecting melanogenesis, was also negatively correlated with the expression of UCA1. Furthermore, the transcription factor CRE-binding protein (CREB), which promotes MITF expression, was negatively regulated by UCA1. The cAMP/ protein kinase A (PKA), extracellular signaleregulated kinase (ERK), and c-Jun N-terminal kinase (JNK) signaling pathways, which are upstream of the CREB/MITF/melanogenesis axis, were activated or inhibited in response to silencing or enhancing UCA1 expression, respectively. In addition, enhanced UCA1 expression downregulates the expression of melanogenesis-related genes induced by UVB in melanocytes. In conclusion, UCA1 may negatively regulate the CREB/MITF/melanogenesis axis through inhibiting the cAMP/PKA, ERK, and JNK signaling pathways in melanocytes. UCA1 may be a potential therapeutic target for the treatment of pigmented skin diseases.

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“…Mitf has many subtypes [22] , in which type M is specifically expressed in melanocytes [23] , by direct association with related pigmentases such as tyrosinase (Tyr), dopachrome tautomerase (Dct), endothelin receptor type B (Ednrb), solute carrier family 45 member 2 (Slc45a2), regulating the survival, migration and differentiation of melanocytes [24] . Among them, Mitf-M gene [23,25,26] plays a key role in regulating tyrosine metabolic pathway and melanin production, mainly regulating downstream pigment-related enzymes such as Tyr, Dct, Tyrp1, etc. Mitf-M also controls cytoskeleton and intercellular tight protein to regulate morphology and migration of melanocytes.…”

Section: Discussionmentioning

confidence: 99%

Transcript profiles of stria vascularis in models of Waardenburg syndrome

Chen

Wang

Chen

et al. 2019

Preprint

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Background: Waardenburg syndrome is a common syndromic hereditary deafness disease caused by stria vascularis dysfunction. However, the genetic pathway affecting stria vascularis development is still not clear. In this paper, the transcript profile of stria vascularis of Waardenburg syndrome was studied using Mitf-M mutant pigs and mice models. GO analysis was performed to identify the differential gene expression caused by Mitf-M mutation. Results: There were over than one hundred genes mainly found in tyrosine metabolism, melanin formation and ion transportations showed significant changes in both models. In addition, there were some spiced specific gene changes in the stria vascularis in the mouse and porcine models. The expression of tight junction-associated genes, including Cadm1, Cldn11, Pcdh1, Pcdh19 and Cdh24 genes, were significantly higher in porcine models compared to mouse models. Vascular-related and ion channel-related genes in the stria vascularis were also shown significantly difference between the two species. The expression of Col2a1, Col3a1, Col11a1 and Col11a2 genes were higher and the expression of Col8a2, Cd34 and Ncam genes were lower in the porcine model compared to mouse model. In both models, Trpm1, Kcnj13, and Slc45a2 genes were both affected by the Mitf-M mutation. In the pig models, the expression of Kcnn1, Clcn2 and Trpm4 genes were higher than the mouse model; whereas the expression of Trpm7, Kcnq1 and Kcnj8 genes were higher in the mouse models than the pig models. However, there was no significant difference in the morphology of the stria vascularis between these two models. Conclusions: Our data suggests that there is a significant difference on the gene expression and function between these two models.

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MITF-M regulates melanogenesis in mouse melanocytes

Abstract: These results directly demonstrate that MITF-M not only influences melanogenesis, but also determines the progression of melanosomal protein in mouse melanocytes.

Cited by 37 publications

References 56 publications

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)

The Long Noncoding RNA UCA1 Negatively Regulates Melanogenesis in Melanocytes

Transcript profiles of stria vascularis in models of Waardenburg syndrome

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