Dimethyl Itaconate Reduces α-MSH-Induced Pigmentation via Modulation of AKT and p38 MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells

Jang, Sungchan; Chi, Won-Jae; Kim, Seung-Young

doi:10.3390/molecules27134183

Cited by 4 publications

(3 citation statements)

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“…In brief, the α-MSH-cAMP-CREB, Wnt/β-catenin, and MAPK signaling pathways are inhibited, resulting in the downregulation of MITF expression within the dorsal skin of D0 goslings. This inhibition results in decreased expression of melanogenesis genes such as dopachrome tautomerase (DCT), tyrosinase (TYR ), and tyrosinaserelated protein 1 (TYRP1) in melanocytes [64][65][66], as observed in our RNA-seq and qRT-PCR analyses. A similar study indicated a significant decrease in the expression of these genes from E15 to E28 in geese [67], and these genes became undetectable by E29.…”

Section: Discussionsupporting

confidence: 62%

Transcriptome analysis of sexual dimorphism in dorsal down coloration in goslings

Liu,

Li,

Guo

et al. 2024

BMC Genomics

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Background In day-old Hungarian white goose goslings, there is a noticeable difference in dorsal down coloration between males and females, with females having darker dorsal plumage and males having lighter plumage. The ability to autosex day-old goslings based on their dorsal down coloration is important for managing them efficiently and planning their nutrition in the poultry industry. The aim of this study was to determine the biological and genetic factors underlying this difference in dorsal down colorationthrough histological analysis, biochemical assays, transcriptomic profiling, and q‒PCR analysis. Results Tissue analysis and biochemical assays revealed that compared with males, 17-day-old embryos and day-old goslings of female geese exhibited a greater density of melanin-containing feather follicles and a greater melanin concentration in these follicles during development. Both female and male goslings had lower melanin concentrations in their dorsal skin compared to 17-day-old embryos. Transcriptome analysis identified a set of differentially expressed genes (DEGs) (MC1R, TYR, TYRP1, DCT and MITF) associated with melanogenesis pathways that were downregulated or silenced specifically in the dorsal skin of day-old goslings compared to 17-day-old embryos, affecting melanin synthesis in feather follicles. Additionally, two key genes (MC1R and MITF) associated with feather coloration showed differences between males and females, with females having higher expression levels correlated with increased melanin synthesis and darker plumage. Conclusion The expression of multiple melanogenesis genes determines melanin synthesis in goose feather follicles. The dorsal down coloration of day-old Hungarian white goose goslings shows sexual dimorphism, likely due to differences in the expression of the MC1R and MITF genes between males and females. These results could help us better understand why male and female goslings exhibit different plumage patterns.

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Section: Discussionsupporting

confidence: 62%

Transcriptome analysis of sexual dimorphism in dorsal down coloration in goslings

Liu,

Li,

Guo

et al. 2024

BMC Genomics

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“…Previously, Shin et al have demonstrated that adenoviral expression of NRF2 or treatment of wortmannin using as an inhibitor of the PI3K/AKT signaling pathway suppressed melanogenesis in normal human melanocytes (NHMCs) [ 37 ]. On the other hand, Jang et al have demonstrated that treatment of DMI reduced α-MSH-induced pigmentation by increasing AKT activation phosphorylation at Ser473 in B16F10 cells [ 38 ]. While the role of the PI3K/AKT pathway in the inhibition of melanogenesis by DMI is still enigmatic, we have demonstrated that DMI inhibits MITF ( Figure 3 ) and its melanogenic targets such as TYR, TRP-1, and TRP-2 ( Figure 2 ) by affecting the α-MSH/MC1R-ERK1/2-MITF axis ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

Dimethyl Itaconate Inhibits Melanogenesis in B16F10 Cells

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Choi

et al. 2023

Antioxidants

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Itaconate is a metabolite produced to counteract and resolve pro-inflammatory responses when macrophages are challenged with intracellular or extracellular stimuli. In the present study, we have observed that dimethyl itaconate (DMI) inhibits melanogenesis in B16F10 cells. DMI inhibits microphthalmia-associated transcription factor (MITF) and downregulates the expression of MITF target genes, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). DMI also decreases the level of melanocortin 1 receptor (MC1R) and the production of α-melanocyte stimulating hormone (α-MSH), resulting in the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and MITF activities. The structure–activity relationship (SAR) study illustrates that the α,β-unsaturated carbonyl moiety in DMI, a moiety required to target KELCH-like ECH-associated protein 1 (KEAP1) to activate NF-E2-related factor 2 (NRF2), is necessary to inhibit melanogenesis and knocking down Nrf2 attenuates the inhibition of melanogenesis by DMI. Together, our study reveals that the MC1R-ERK1/2-MITF axis regulated by the KEAP1-NRF2 pathway is the molecular target responsible for the inhibition of melanogenesis by DMI.

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“…Consistent with our ndings, several previous studies [23,[26][27][28][29] have reported similar results from transcriptome and RNA-seq analysis of poultry skin feather follicles, demonstrating a notable enrichment of genes in both the Wnt signaling pathway and melanogenesis process. These signaling pathways play a pivotal role in the development of melanocytes and melanin biosynthesis [30][31][32], regulating the expression of key regulatory factors like melanocortin 1 receptor (MC1R), dopachrome tautomerase (DCT), tyrosinase(TYR), tyrosinase-related protein 1 (TYRP1), and microphthalmia transcription factor (MITF), thereby determining the levels of melanin production [33][34][35]. In our RNA-seq and qRT-PCR analysis, we observed a signi cant down-regulation or even silencing of these gene expressions within the dorsal skin of day-old goslings (Fig.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Sexual Dimorphism in Dorsal Down Coloration in Goslings

Liu,

Li,

Guo

et al. 2023

Preprint

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Background Distinctive sexual dimorphism in dorsal down coloration is apparent in day-old Hungarian white goose goslings, characterized by darker dorsal plumage in females and lighter plumage in males. The ability to autosex day-old goslings based on their dorsal down coloration is crucial for efficient management and nutrition strategies in the poultry industry. The objective of this research was to gain a deeper understanding of the potential biological and genetic mechanisms governing sexually dimorphic down coloration in geese, utilizing tissue slice analysis, biochemical assays, transcriptomic profiling, and q-PCR analysis. Results The tissue slice and biochemical results revealed that female geese exhibited a higher density of melanin-containing feather follicles and a greater concentration of melanin within these follicles compared to male geese during embryonic development at 17 days and in day-old goslings. Both female and male individuals, in comparison to 17-day goose embryos, showed a significant decrease in melanin concentrations in the dorsal skin of day-old goslings. Through transcriptome analysis, we identified a set of differentially expressed genes (DEGs) (MC1R, TYR, TYRP1, DCT and MITF) associated with Melanogenesis pathways that exhibit substantial down-regulation or complete silencing specifically within the dorsal skin of day-old goslings when compared to 17-day embryos. This resulting in impaired melanin synthesis in the feather follicle. Additionally, sexual dimorphism in feather coloration is associated with two key DEGs (MC1R and MITF). Female geese exhibited higher expression levels of MC1R and MITF, positively correlated with increased melanin synthesis and deposition, resulting in a more pronounced plumage phenotype characterized by darker coloration. Conclusions Melanin synthesis in goose feather follicles was determined by the expression of multiple melanogenesis genes. Sexual dimorphism in dorsal down coloration of day-old Hungarian white goose goslings was contingent upon two essential MC1R and MITF genes. Our research lays the essential foundation for advancing the breeding in autosexing geese, promising substantial benefits to breeders and producers.

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Dimethyl Itaconate Reduces α-MSH-Induced Pigmentation via Modulation of AKT and p38 MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells

Cited by 4 publications

References 58 publications

Transcriptome analysis of sexual dimorphism in dorsal down coloration in goslings

Transcriptome analysis of sexual dimorphism in dorsal down coloration in goslings

Dimethyl Itaconate Inhibits Melanogenesis in B16F10 Cells

Transcriptome Analysis of Sexual Dimorphism in Dorsal Down Coloration in Goslings

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