Single-cell sequencing reveals the antifibrotic effects of YAP/TAZ in systemic sclerosis

Wu, Dongke; Wang, Wei; Li, Xinyue; Yin, Baoshu; Ma, Yunqing

doi:10.1016/j.biocel.2022.106257

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…One of these substances -celastrol -was also effective in bleomycin-induced skin fibrosis with reductions in dermal thickness, myofibroblast differentiation and in the spatial expression of pro-fibrotic markers [68]. Another study also demonstrated that knockdown of either YAP or TAZ or both combined ameliorated bleomycin-induced dermal as well as lung fibrosis [69].…”

Section: Mechanosensing and Transductionmentioning

confidence: 99%

Mechanisms of Fibroblast Activation during Fibrotic Tissue Remodeling

Rius Rigau,

Dees

2024

Fibrosis

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Fibrosis can occur in almost every organ system. It can occur in single organs, such as in idiopathic pulmonary fibrosis (IPF), or affect multiple organs as in systemic sclerosis (SSc). Fibrotic diseases are recognized as major cause of morbidity and mortality in modern societies due to the dysfunction or loss of function of the affected organs. This dysfunction is caused by progressive deposition of extracellular matrix proteins released by activated fibroblasts. Activation of fibroblasts and differentiation into myofibroblasts is required for physiological tissue remodeling, e.g, during wound healing. Disruption of regulatory mechanisms, however, results in chronic and uncontrolled activity of fibroblasts and myofibroblasts. Intensive research during the past years identified several core pathways of pathophysiological relevance, and described different fibroblast subsets based on their expression profile in fibrotic tissue. Herein, we discuss the molecular changes in fibroblasts leading to persistent activation during fibrotic tissue remodeling with a focus on lung fibrosis and SSc.

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Section: Mechanosensing and Transductionmentioning

confidence: 99%

Mechanisms of Fibroblast Activation during Fibrotic Tissue Remodeling

Rius Rigau,

Dees

2024

Fibrosis

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“…However, YAP/TAZ mechanosignaling in stromal cells has also been implicated in tissue fibrosis [115,116]. Nuclear expression of YAP/TAZ is high in affected tissues in human fibrotic diseases (e.g., idiopathic pulmonary fibrosis [IPF] and systemic sclerosis) [117][118][119] and experimentally-induced fibrotic conditions (e.g., myocardial infarction, diabetes, and chronic colitis) in mice [120][121][122][123][124]. In addition, pharmacological disruption of YAP-TEAD interaction using verteporfin reduces fibrosis in a mouse model of cardiac fibrosis and fibrotic renal injury [116,121].…”

Section: Figure 2 Role Of Yap/taz In Mechanosensing Induced By Stroma...mentioning

confidence: 99%

YAP/TAZ as Molecular Targets in Skeletal Muscle Atrophy and Osteoporosis

Kwon

2024

Aging and disease

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Skeletal muscles and bones are closely connected anatomically and functionally. Age-related degeneration in these tissues is associated with physical disability in the elderly and significantly impacts their quality of life. Understanding the mechanisms of age-related musculoskeletal tissue degeneration is crucial for identifying molecular targets for therapeutic interventions for skeletal muscle atrophy and osteoporosis. The Hippo pathway is a recently identified signaling pathway that plays critical roles in development, tissue homeostasis, and regeneration. The Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key downstream effectors of the mammalian Hippo signaling pathway. This review highlights the fundamental roles of YAP and TAZ in the homeostatic maintenance and regeneration of skeletal muscles and bones. YAP/TAZ play a significant role in stem cell function by relaying various environmental signals to stem cells. Skeletal muscle atrophy and osteoporosis are related to stem cell dysfunction or senescence triggered by YAP/TAZ dysregulation resulting from reduced mechanosensing and mitochondrial function in stem cells. In contrast, the maintenance of YAP/TAZ activation can suppress stem cell senescence and tissue dysfunction and may be used as a basis for the development of potential therapeutic strategies. Thus, targeting YAP/TAZ holds significant therapeutic potential for alleviating age-related muscle and bone dysfunction and improving the quality of life in the elderly.

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“…Single-cell sequencing identified YAP as a potential therapeutic target for SSc. 29 Transcriptome analysis in a scleroderma model showed that YAP knockdown resulted in the downregulation of the profibrotic genes TGF-β1, endothelin 1 (ET-1), IL-6, TEAD1, plasminogen activator inhibitor 1 (PAI-1), cysteine-rich 61 (Cyr61/CCN1), and CCN2. 30 As a critical effector of mechanotransduction signaling, YAP nuclear accumulation and activity increased with matrix stiffness and in fibroblasts; a pathologic increase in ECM stiffness activated YAP, inducing the expression of profibrotic mediators such as PAI-1 and ECM proteins, leading to fibroblast activation and tissue fibrosis.…”

Section: Role Of Yap In Sclerodermamentioning

confidence: 99%

“…High YAP expression promotes skin thickening and fibrosis in systemic sclerosis (SSc) as a result of EMT of skin epithelial cells to fibroblasts (mesenchymal‐like cells). Single‐cell sequencing identified YAP as a potential therapeutic target for SSc 29 . Transcriptome analysis in a scleroderma model showed that YAP knockdown resulted in the downregulation of the profibrotic genes TGF‐β1, endothelin 1 (ET‐1), IL‐6, TEAD1, plasminogen activator inhibitor 1 (PAI‐1), cysteine‐rich 61 (Cyr61/CCN1), and CCN2 30 .…”

Section: Relationship Between Yap and Skin Diseasesmentioning

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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Single-cell sequencing reveals the antifibrotic effects of YAP/TAZ in systemic sclerosis

Cited by 4 publications

References 35 publications

Mechanisms of Fibroblast Activation during Fibrotic Tissue Remodeling

Mechanisms of Fibroblast Activation during Fibrotic Tissue Remodeling

YAP/TAZ as Molecular Targets in Skeletal Muscle Atrophy and Osteoporosis

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

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