IL-17A Promotes Psoriasis-Associated Keratinocyte Proliferation through ACT1-Dependent Activation of YAP–AREG Axis

Yu, Zengyang; Yu, Qian; Xu, Hui; Dai, Xing; Yu, Yingyuan; Cui, Lian; Chen, Youdong; Gu, Jun; Zhang, Xilin; Guo, Chunyuan; Shi, Yujun

doi:10.1016/j.jid.2022.02.016

Cited by 34 publications

(15 citation statements)

References 36 publications

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“…This mechanism has been shown to facilitate cell proliferation in psoriasis. 126 Furthermore, glucocorticoid receptor signalling has been shown to participate in the regulation of the Hippo pathway. Glucocorticoids were shown to elevate the expression of fibronectin, thus leading to cytoskeletondependent YAP activation in human breast cancer.…”

Section: Key Components Of the Hippo Pathwaymentioning

confidence: 99%

“…In addition, in human and mouse skin, YAP-TEAD activation promotes the proliferation of keratinocytes to maintain skin homoeostasis 154,155 or mediate IL-17A-driven psoriasis. 126 Moreover, the Hippo pathway regulates contactdependent cell growth and proliferation in cancer cells, 156,157 nervous Schwann cells, 158 epidermal stem cells 159 and hepatic 160 or lung epithelial cells. 161,162 In addition to the role of the Hippo pathway in cell growth/ proliferation control, this pathway has also been shown to affect specific cell differentiation in a variety of tissues and organs, including the pancreas, lung, muscle and mammary glands.…”

Section: Critical Physiological Functions Of the Hippo Pathwaymentioning

confidence: 99%

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The Hippo signalling pathway and its implications in human health and diseases

Lan

et al. 2022

Sig Transduct Target Ther

231

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As an evolutionarily conserved signalling network, the Hippo pathway plays a crucial role in the regulation of numerous biological processes. Thus, substantial efforts have been made to understand the upstream signals that influence the activity of the Hippo pathway, as well as its physiological functions, such as cell proliferation and differentiation, organ growth, embryogenesis, and tissue regeneration/wound healing. However, dysregulation of the Hippo pathway can cause a variety of diseases, including cancer, eye diseases, cardiac diseases, pulmonary diseases, renal diseases, hepatic diseases, and immune dysfunction. Therefore, therapeutic strategies that target dysregulated Hippo components might be promising approaches for the treatment of a wide spectrum of diseases. Here, we review the key components and upstream signals of the Hippo pathway, as well as the critical physiological functions controlled by the Hippo pathway. Additionally, diseases associated with alterations in the Hippo pathway and potential therapies targeting Hippo components will be discussed.

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Section: Key Components Of the Hippo Pathwaymentioning

confidence: 99%

Section: Critical Physiological Functions Of the Hippo Pathwaymentioning

confidence: 99%

The Hippo signalling pathway and its implications in human health and diseases

Lan

et al. 2022

Sig Transduct Target Ther

231

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“…Interestingly, recent research has revealed that CHAC1, like SLC7A11, is downregulated by the loss of YAP/TAZ, inducing ferroptosis [ 40 ]. In psoriasis, YAP signaling is activated by IL-17A, promoting keratinocyte proliferation [ 41 ]. However, the role of CHAC1 in the execution of ferroptosis and its involvement in psoriasis is unclear.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Identification of Ferroptosis-Associated Biomarkers and Therapeutic Compounds in Psoriasis

Mao

2022

Journal of Oncology

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Purpose. Psoriasis is closely linked to ferroptosis. This study aimed to identify potential ferroptosis-associated genes in psoriasis using bioinformatics. Methods. Data from the GSE30999 dataset was downloaded from the Gene Expression Omnibus (GEO), and the ferroptosis-associated genes were retrieved from FerrDb. The differentially expressed ferroptosis-associated genes were identified using Venn diagrams. Subsequently, a network of protein-protein interactions (PPIs) between psoriasis targets and ferroptosis-associated genes was constructed based on the STRING database and analyzed by Cytoscape software. The Metascape portal conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Moreover, the expression of ferroptosis-related genes was verified in the GSE13355 dataset. Finally, the verified genes were used to predict the therapeutic drugs for psoriasis using the DGIdb/CMap database. SwissDock was used to examine ligand docking, and UCSF Chimera displayed the results visually. Results. Among 85 pairs of psoriasis lesion (LS) and no-lesion (NL) samples from patients, 19 ferroptosis-associated genes were found to be differentially expressed (3 upregulated genes and 16 downregulated genes). Based on the PPI results, these ferroptosis-associated genes interact with each other. The GO and KEGG enrichment analysis of differentially expressed ferroptosis-related genes indicated several enriched terms related to the oxidative stress response. The GSE13355 dataset verified the results of the bioinformatics analysis obtained from the GSE30999 dataset regarding SLC7A5, SLC7A11, and CHAC1. Psoriasis-related compounds corresponding to SLC7A5 and SLC7A11 were also identified, including Melphalan, Quisqualate, Riluzole, and Sulfasalazine. Conclusion. We identified 3 differentially expressed ferroptosis-related genes through bioinformatics analysis. SLC7A5, SLC7A11, and CHAC1 may affect the development of psoriasis by regulating ferroptosis. These results open new avenues in understanding the treatment of psoriasis.

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“…33 IL-17α was shown to promote the development of psoriasis via activation of the YAP/AREG axis. 34 Meanwhile, IL-38 inhibited the transcriptional activity of YAP to suppress keratinocyte proliferation. 35 Inhibiting YAP expression improved skin lesions by inducing cell cycle arrest in G0/G1 phase and reducing the levels of inflammatory factors as well as activation of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B signaling.…”

Section: Role Of Yap In Psoriasismentioning

confidence: 99%

Recent advances in the role of Yes‐associated protein in dermatosis

Jia

Liu

2023

Skin Research and Technology

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Background: Dermatosis is a general term for diseases of the skin and skin appendages including scleroderma, psoriasis, bullous disease, atopic dermatitis, basal cell carcinoma, squamous cell carcinoma, and melanoma. These diseases affect millions of individuals globally and are a serious public health concern. However, the pathogenesis of skin diseases is not fully understood, and treatments are not optimal. Yes-associated protein (YAP) is a transcriptional coactivator that plays a role in the regulation of gene transcription and signal transduction. Aims:To study the role of Yes-associated protein in skin diseases. Materials and Methods:The present review summarizes recent advances in our understanding of the role of YAP in skin diseases, current treatments that target YAP, and potential avenues for novel therapies.Results: Abnormal YAP expression has been implicated in occurrence and development of dermatosis. YAP regulates the cell homeostasis, proliferation, differentiation, apoptosis, angiopoiesis, and epithelial-to-mesenchymal transition, among other processes. As well as, it serves as a potential target in many biological processes for treating dermatosis. Conclusions:The effects of YAP on the skin are complex and require multidimensional investigational approaches. YAP functions as an oncoprotein that can promote the occurrence and development of cancer, but there is currently limited information on the therapeutic potential of YAP inhibition for cancer treatment. Additional studies are also needed to clarify the role of YAP in the development and maturation of dermal fibroblasts; skin barrier function, homeostasis, aging, and melanin production; and dermatosis.

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IL-17A Promotes Psoriasis-Associated Keratinocyte Proliferation through ACT1-Dependent Activation of YAP–AREG Axis

Cited by 34 publications

References 36 publications

The Hippo signalling pathway and its implications in human health and diseases

The Hippo signalling pathway and its implications in human health and diseases

Bioinformatics Identification of Ferroptosis-Associated Biomarkers and Therapeutic Compounds in Psoriasis

Recent advances in the role of Yes‐associated protein in dermatosis

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