Hippo-Yap/Taz signalling in zebrafish regeneration

Riley, Susanna E.; Feng, Yi

doi:10.1038/s41536-022-00209-8

Cited by 24 publications

(11 citation statements)

References 311 publications

(268 reference statements)

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“…This process of Glial EMT is indispensable sufficient to initiate glial bridging. This phenomenon is closely associated with the Yap1-Ctgfa signalling pathway, also recognized as the HIPPO signalling pathway (59).…”

Section: Discussionmentioning

confidence: 89%

“…In the context of regeneration following injury, the HIPPO pathway undergoes inactivation, leading to the activation of Yap1. Subsequently, Yap1 undergoes cytoplasm-to-nuclear translocation, initiating the transcription of pro-proliferative genes, such as ctgfa (59) . Henceforth, we postulate that Sirt1 facilitates Dnmt1mediated demethylation or hypomethylation of Yap1 at the transcriptional level, thereby activating Yap1 and promoting its nuclear translocation.…”

Section: As Glial Epithelial-to-mesenchymal Transition (Emt) Is Intri...mentioning

confidence: 99%

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Epigenetic cross-talk between Sirt1 and Dnmt1 promotes axonal regeneration after spinal cord injury in zebrafish

Gupta,

Hui

2024

Preprint

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Though spinal cord injury (SCI) causes irreversible sensory and motor impairments in human, adult zebrafish retain the potent regenerative capacity by injury-induced proliferation of central nervous system (CNS)-resident progenitor cells to develop new functional neurons at the lesion site. The hallmark of SCI in zebrafish lies in a series of changes in the epigenetic landscape, specifically DNA methylation and histone modifications. Decoding the post-SCI epigenetic modifications is therefore critical for the development of therapeutic remedies that boost SCI recovery process. Here, we have studied on Sirtuin1 (Sirt1), a non-classical histone deacetylase that potentially play a critical role in neural progenitor cells (NPCs) proliferation and axonal regrowth following SCI in zebrafish. We investigated the role of Sirt1 in NPC proliferation and axonal regrowth in response to injury in the regenerating spinal cord and found that Sirt1 is involved in the induction of NPC proliferation along with glial bridging during spinal cord regeneration. We also demonstrate that Sirt1 plays a pivotal role in regulating the HIPPO pathway through deacetylation-mediated inactivation of Dnmt1 and subsequent hypomethylation of yap1 promoter, leading to the induction of ctgfa expression, which drives the NPC proliferation and axonal regrowth to complete the regenerative process. In conclusion, our study reveals a novel cross-talk between two important epigenetic effectors, Sirt1 and Dnmt1, in the context of spinal cord regeneration, establishing a previously undisclosed relation between Sirt1 and Yap1 which provides a deeper understanding of the underlying mechanisms governing injury-induced NPC proliferation and axonal regrowth. Therefore, we have identified Sirt1 as a novel, major epigenetic regulator of spinal cord regeneration by modulating the HIPPO pathway in zebrafish.

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Section: Discussionmentioning

confidence: 89%

Section: As Glial Epithelial-to-mesenchymal Transition (Emt) Is Intri...mentioning

confidence: 99%

Epigenetic cross-talk between Sirt1 and Dnmt1 promotes axonal regeneration after spinal cord injury in zebrafish

Gupta,

Hui

2024

Preprint

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“…[70] To our knowledge, the Hippo pathway is a highly conserved signal transduction pathway programming gene expression, the core effectors of which are the homologous transcriptional co-activators YAP and TAZ. [71,72] YAP/TAZ signaling stimulates the expression of a range of proliferative, oncogenic, and epithelial-mesenchymal transition (EMT) genes through nuclear localization and binding to the transcription factor TEA domain transcription factor (TEAD1). [73] Besides, by combining the evidence provided by transcriptome analysis and validation at the protein level, we also observed the activation of Jun N-terminal kinase and the downregulation of p53/p21 signaling.…”

Section: Discussionmentioning

confidence: 99%

An H₂S‐BMP6 Dual‐Loading System with Regulating Yap/Taz and Jun Pathway for Synergistic Critical Limb Ischemia Salvaging Therapy

Liao

et al. 2023

Adv Healthcare Materials

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Critical limb ischemia, the final course of peripheral artery disease, is characterized by an insufficient supply of blood flow and excessive oxidative stress. H2S molecular therapy possesses huge potential for accelerating revascularization and scavenging intracellular reactive oxygen species (ROS). Moreover, it is found that BMP6 is the most significantly up‐expressed secreted protein‐related gene in HUVECs treated with GYY4137, a H2S donor, based on the transcriptome analysis. Herein, a UIO‐66‐NH2@GYY4137@BMP6 co‐delivery nanoplatform to strengthen the therapeutic effects of limb ischemia is developed. The established UIO‐66‐NH2@GYY4137@BMP6 nanoplatform exerts its proangiogenic and anti‐oxidation functions by regulating key pathways. The underlying molecular mechanisms of UIO‐66‐NH2@GYY4137@BMP6 dual‐loading system lie in the upregulation of phosphorylated YAP/TAZ and Jun to promote HUVECs proliferation and downregulation of phosphorylated p53/p21 to scavenge excessive ROS. Meanwhile, laser‐doppler perfusion imaging (LDPI), injury severity evaluation, and histological analysis confirm the excellent therapeutic effects of UIO‐66‐NH2@GYY4137@BMP6 in vivo. This work may shed light on the treatment of critical limb ischemia by regulating YAP, Jun, and p53 signaling pathways based on gas‐protein synergistic therapy.

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“…YAP, which stands for Yes-associated protein, is a multifunctional cellular transcription factor. [13][14][15] During normal cell development, YAP enters the nucleus and binds to its transcription factor TEAD, promoting the expression of downstream target genes. This leads to the promotion of cell growth and inhibition of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

α‐Catenin promotes dermal fibroblasts proliferation and migration during wound healing via FAK/YAP activation

Wang,

Xu,

Guan

et al. 2024

The FASEB Journal

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Skin wound healing is a complex and organized biological process, and the dermal fibroblasts play a crucial role. α‐Catenin is known to be involved in regulating various cellular signals, and its role in wound healing remains unclear. Here, we have identified the pivotal role of the α‐catenin/FAK/YAP signaling axis in the proliferation and migration of dermal fibroblasts, which contributes to the process of skin wound healing. Briefly, when α‐catenin was knocked down specifically in dermal fibroblasts, the wound healing rate is significantly delayed. Moreover, interfering with α‐catenin can impede the proliferation and migration of dermal fibroblasts both in vitro and in vivo. Mechanistically, the overexpression of α‐catenin upregulates the nuclear accumulation of YAP and transcription of downstream target genes, resulting in enhanced the proliferation and migration of dermal fibroblasts. Furthermore, the FAK Tyr397 phosphorylation inhibitor blocked the promoting effects of α‐catenin on YAP activation. Importantly, the continuous phosphorylation mutation of FAK Tyr397 reversed the retardatory effects of α‐catenin knockdown on wound healing, by increasing the vitality of fibroblasts. Likewise, α‐catenin/FAK was validated as a therapeutic target for wound healing in the db/db chronic trauma model. In summary, our findings have revealed a novel mechanism by which α‐catenin facilitates the function of fibroblasts through the activity of the FAK/YAP signaling axis. These findings define a promising therapeutic strategy for accelerating the wound healing process.

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Hippo-Yap/Taz signalling in zebrafish regeneration

Cited by 24 publications

References 311 publications

Epigenetic cross-talk between Sirt1 and Dnmt1 promotes axonal regeneration after spinal cord injury in zebrafish

Epigenetic cross-talk between Sirt1 and Dnmt1 promotes axonal regeneration after spinal cord injury in zebrafish

An H₂S‐BMP6 Dual‐Loading System with Regulating Yap/Taz and Jun Pathway for Synergistic Critical Limb Ischemia Salvaging Therapy

α‐Catenin promotes dermal fibroblasts proliferation and migration during wound healing via FAK/YAP activation

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Hippo-Yap/Taz signalling in zebrafish regeneration

Cited by 24 publications

References 311 publications

Epigenetic cross-talk between Sirt1 and Dnmt1 promotes axonal regeneration after spinal cord injury in zebrafish

Epigenetic cross-talk between Sirt1 and Dnmt1 promotes axonal regeneration after spinal cord injury in zebrafish

An H2S‐BMP6 Dual‐Loading System with Regulating Yap/Taz and Jun Pathway for Synergistic Critical Limb Ischemia Salvaging Therapy

α‐Catenin promotes dermal fibroblasts proliferation and migration during wound healing via FAK/YAP activation

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An H₂S‐BMP6 Dual‐Loading System with Regulating Yap/Taz and Jun Pathway for Synergistic Critical Limb Ischemia Salvaging Therapy