ERK inhibitor JSI287 alleviates imiquimod-induced mice skin lesions by ERK/IL-17 signaling pathway

Huang, Xiaoling; Yu, Peilin; Liu, Minyu; Deng, Yi-Fang; Dong, Yuqiong; Quan-hai, Liu; Zhang, Jintao; Wu, Tong

doi:10.1016/j.intimp.2018.11.031

Cited by 25 publications

(13 citation statements)

References 29 publications

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“…A significant correlation was also observed between the ERK1/2 signaling pathway and GSC stemness 33 . Both GDF15 and IMQ can activate the ERK1/ 2 signaling pathway [39][40][41][42] , which is also involved in the transcription of LIF 43,44 . Here, we showed that ERK1/2 activation might be a critical upstream event in the induction of LIF expression by GDF15.…”

Section: Discussionmentioning

confidence: 99%

GDF15 promotes glioma stem cell-like phenotype via regulation of ERK1/2–c-Fos–LIF signaling

et al. 2021

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Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β family, is associated with tumor progression, metastasis, and cell apoptosis. However, controversy persists regarding the role of GDF15 in different tumor types, and its function in glioma stem cells (GSCs) remains unknown. Here, we report that GDF15 promotes the GSC-like phenotype in GSC-like cells (GSCLCs) through the activation of leukemia inhibitor factor (LIF)–STAT3 signaling. Mechanistically, GDF15 was found to upregulate expression of the transcription factor c-Fos, which binds to the LIF promoter, leading to enhanced transcription of LIF in GSCLCs. Furthermore, GDF15 may activate the ERK1/2 signaling pathway in GSCLCs, and the upregulation of LIF expression and the GSC-like phenotype was dependent on ERK1/2 signaling. In addition, the small immunomodulator imiquimod induced GDF15 expression, which in turn activated the LIF–STAT3 pathway and subsequently promoted the GSC-like phenotype in GSCLCs. Thus, our results demonstrate that GDF15 can act as a proliferative and pro-stemness factor for GSCs, and therefore, it may represent a potential therapeutic target in glioma treatment.

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Section: Discussionmentioning

confidence: 99%

GDF15 promotes glioma stem cell-like phenotype via regulation of ERK1/2–c-Fos–LIF signaling

et al. 2021

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“…found that glycyrrhizin ameliorated imiquimod-induced psoriasis-like skin lesions in mice and TNF-α-induced ICAM-1 expression in HaCaT cells by the suppression of MAPKs. Other studies also suggested that the suppression of p38 [ 46 , 47 ], JNK [ 48 , 49 ] or ERK [ 50 , 51 ] signaling pathway all contribute to the protection of psoriasis associated symptoms. In the present work, we found that pretreatment of catalpol decreased IMQ-induced or TNF-α-stimulated excitation of ERK, JNK, and p38 in a dose-dependent manner in psoriatic lesioned skin or human keratinocytes, respectively.…”

Section: Discussionmentioning

confidence: 99%

Catalpol ameliorates psoriasis-like phenotypes via SIRT1 mediated suppression of NF-κB and MAPKs signaling pathways

et al. 2020

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Psoriasis is a chronic inflammatory skin disease that affects approximately 2% of worldwide population, and causing long-term troubles to the patients. Therefore, it is urgent to develop safe and effective therapeutic drugs. Catalpol is a natural iridoid glucoside, that has several remarkable pharmacological effects, however, whether catalpol can alleviated psoriasis has not been explored. The goal of the present work is to study the role of catalpol in psoriasis in vivo and in vitro. Imiquimod-induced psoriasislike mice were applied with different concentrations of catalpol for 8 consecutive days. The severity degree of psoriasis was estimated and the skin pathological changes were detected by H&E staining. Also, TNF-α-stimulated keratinocytes were treated with different concentrations of catalpol, then the oxidative stress and inflammation factors, as well as the expression of SIRT1 and activation of NF-kB and MAPK pathways were measured. The results showed that catalpol reduced the erythema, scaling, ear thickness, and changed pathological phenotypes in the lesioned skin region in mice. Treatment with catalpol significantly suppressed the oxidative stress and inflammatory reactions in vivo and in vitro, as reflected by the decreased secretion or expression of oxidative stress indicators and proinflammatory factors. Furthermore, the SIRT1 was up-regulated and the NF-κB and MAPKs signaling pathways were suppressed by the treatment of catalpol in vivo and in vitro. In summary, our data suggested that catalpol may have a therapeutic property of psoriasis by ameliorating oxidative stress and inflammation partly through SIRT1 mediated suppression of NF-κB and MAPKs pathways.

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“…Like p38, ERK1/2 was also activated in the epidermis of psoriatic patients [ 88 ]. Inhibition of ERK by a specific ERK inhibitor JSI287 decreased IMQ-induced psoriasiform lesion [ 89 ]. DUSP1/MKP-1, a member of the dual-specificity phosphatase family, acts as a negative regulator of MAPK pathway.…”

Section: Factors Regulating Psoriatic Keratinocytesmentioning

confidence: 99%

Advances in the pathogenesis of psoriasis: from keratinocyte perspective

et al. 2022

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Psoriasis is a complex long-lasting inflammatory skin disease with high prevalence and associated comorbidity. It is characterized by epidermal hyperplasia and dermal infiltration of immune cells. Here, we review the role of keratinocytes in the pathogenesis of psoriasis, focusing on factors relevant to genetics, cytokines and receptors, metabolism, cell signaling, transcription factors, non-coding RNAs, antimicrobial peptides, and proteins with other different functions. The critical role of keratinocytes in initiating and maintaining the inflammatory state suggests the great significance of targeting keratinocytes for the treatment of psoriasis.

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ERK inhibitor JSI287 alleviates imiquimod-induced mice skin lesions by ERK/IL-17 signaling pathway

Cited by 25 publications

References 29 publications

GDF15 promotes glioma stem cell-like phenotype via regulation of ERK1/2–c-Fos–LIF signaling

GDF15 promotes glioma stem cell-like phenotype via regulation of ERK1/2–c-Fos–LIF signaling

Catalpol ameliorates psoriasis-like phenotypes via SIRT1 mediated suppression of NF-κB and MAPKs signaling pathways

Advances in the pathogenesis of psoriasis: from keratinocyte perspective

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