Nrf2 Negatively Regulates Melanogenesis by Modulating PI3K/Akt Signaling

Shin, Jung-Hye; Kim, Mi Yoon; Sohn, Kyung-Ah; Jung, So-Young; Lee, Hae-Eul; Lim, Jae Woo; Kim, Soo-Il; Lee, Young-Ho; Im, Myung; Seo, Young‐Joon; Kim, Chang Deok; Lee, Jeung‐Hoon; Lee, Young; Yoon, Tae‐Jin

doi:10.1371/journal.pone.0096035

Cited by 51 publications

(70 citation statements)

References 23 publications

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“…In this regard, inhibition of Akt in melanoma cells increases melanogenesis pathway, by inducing MITF, meanwhile the inhibition of ERK did not [48, 49]. These previous studies could explain why melanogenesis was induced in A7 but not in C10 and G10.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

et al. 2016

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Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy.

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Section: Discussionmentioning

confidence: 99%

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

et al. 2016

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“…IkBa super-repressor was subcloned into pENTR/CMV-HA vector and adenovirus was made as previously reported46.…”

Section: Methodsmentioning

confidence: 99%

Double-stranded RNA induces inflammation via the NF-κB pathway and inflammasome activation in the outer root sheath cells of hair follicles

Shin

Choi

Sohn

et al. 2017

Sci Rep

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Alopecia areata (AA), a chronic, relapsing, hair-loss disorder, is considered to be a T cell-mediated autoimmune disease. It affects approximately 1.7% of the population, but its precise pathogenesis remains to be elucidated. Despite the recent attention focused on the roles of inflammasomes in the pathogenesis of autoinflammatory diseases, little is known about inflammasome activation in AA. Thus, in this study, we investigated the pattern of NLRP3 inflammasome activation in the outer root sheath (ORS) cells of hair follicles. We found that interleukin (IL)-1β and caspase-1 expression was increased in hair follicle remnants and inflammatory cells of AA tissue specimens. After stimulation of ORS cells with the double-stranded (ds)RNA mimic polyinosinic:polycytidylic acid (poly[I:C]), the activation of caspase-1 and secretion of IL-1β were enhanced. Moreover, NLRP3 knockdown decreased this poly(I:C)-induced IL-1β production. Finally, we found that high-mobility group box 1 (HMGB1) translocated from the nucleus to the cytosol and was secreted into the extracellular space by inflammasome activation. Taken together, these findings suggest that ORS cells are important immunocompetent cells that induce NLRP3 inflammasomes. In addition, dsRNA-induced IL-1β and HMGB1 secretion from ORS cells may contribute to clarifying the pathogenesis and therapeutic targets of AA.

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“…Greater susceptibility to oxidative stress has been reported in melanocytes from patients with vitiligo compared to those from unaffected individuals, which contributes to melanocyte damage in vitiligo (Jimbow et al, 2001;Maresca et al, 1997). We also identified multiple pathways linked with the oxidative stress response in melanocytes, including oxidative phosphorylation (Sahoo et al, 2017;Spiegelman and Elcheva, 2017), PI3K-AKT signaling (Kim et al, 2017;Shin et al, 2014), and NRF-2 (Shin et al, 2014). Therefore, the RNA sequencing data not only indicate the high similarity in transcriptome characteristics between patient iMels and HEMs but also reveal multiple signaling pathways involved in the pathogenesis of vitiligo.…”

Section: In Vitro Characteristics Of Patient Imelsmentioning

confidence: 87%

Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation

Liu

Guo

et al. 2019

Cell Reports

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Graphical Abstract Highlights d Suspensive system enhances efficiency of hiPSC differentiation into melanocytes d hiMelanocyte stem cells in bulge region provide long-term function maintenance d Mature hiMelanocytes integrate into the mouse hair bulb and produce melanin d Patient iMelanocytes reveal multiple vitiligo-associated signaling pathways SUMMARYInduced pluripotent stem cells (iPSCs) are a promising melanocyte source as they propagate indefinitely and can be established from patients. However, the in vivo functions of human iPSC-derived melanocytes (hiMels) remain unknown. Here, we generated hiMels from vitiligo patients using a three-dimensional system with enhanced differentiation efficiency, which showed characteristics of human epidermal melanocytes with high sequence similarity and involved in multiple vitiligo-associated signaling pathways. A modified hair follicle reconstitution assay in vivo showed that MITF + PAX3 + TYRP1 + hiMels were localized in the mouse hair bulb and epidermis and produced melanin up to 7 weeks after transplantation, whereas MITF + PAX3 + TYRP1 À hiMelanocyte stem cells integrated into the bulge-subbulge regions.Overall, these data demonstrate the long-term functions of hiMels in vivo to reconstitute pigmented hair follicles and to integrate into normal regions for both mature melanocytes and melanocyte stem cells, providing an alternative source of personalized cellular therapy for depigmentation.

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Nrf2 Negatively Regulates Melanogenesis by Modulating PI3K/Akt Signaling

Cited by 51 publications

References 23 publications

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

Double-stranded RNA induces inflammation via the NF-κB pathway and inflammasome activation in the outer root sheath cells of hair follicles

Therapeutic Potential of Patient iPSC-Derived iMelanocytes in Autologous Transplantation

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