Role of Hippo-YAP1/TAZ pathway and its crosstalk in cardiac biology

Chen, Xiaoqing; Yuan, Wenchang; Li, Yilang; Luo, Jia; Hou, Ning

doi:10.7150/ijbs.47142

Cited by 18 publications

(10 citation statements)

References 98 publications

(133 reference statements)

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“…In the literature, there are several studies showing an interaction between Wnt, YAP, and BMP pathways, for example, in cardiac, intestinal, and embryonic tissue. ( 42 ) Several BMPs have been identified as direct target genes of the YAP1/TAZ signaling cascade. YAP1‐mediated BMP2 expression critically contributes to the growth of heart atrium.…”

Section: Discussionmentioning

confidence: 99%

Wnt1 Boosts Fracture Healing by Enhancing Bone Formation in the Fracture Callus

Haffner‐Luntzer¹,

Ragipoglu²,

Ahmad³

et al. 2020

Journal of Bone and Mineral Research

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Despite considerable improvement in fracture care, 5%-10% of all fractures still heal poorly or result in nonunion formation. Therefore, there is an urgent need to identify new molecules that can be used to improve bone fracture healing. One activator of the Wnt-signaling cascade, Wnt1, has recently gained attention for its intense osteoanabolic effect on the intact skeleton. The aim of the present study was to investigate whether Wnt1 might be a promising molecule to accelerate fracture healing both in skeletally healthy and osteoporotic mice that display a diminished healing capacity. Transgenic mice for a temporary induction of Wnt1 specifically in osteoblasts (Wnt1-tg) were subjected to femur osteotomy. Non-ovariectomized and ovariectomized Wnt1-tg mice displayed significantly accelerated fracture healing based on a strong increase in bone formation in the fracture callus. Transcriptome profiling revealed that Hippo/yes1-associated transcriptional regulator (YAP)-signaling and bone morphogenetic protein (BMP) signaling pathways were highly enriched in the fracture callus of Wnt1-tg animals. Immunohistochemical staining confirmed increased activation of YAP1 and expression of BMP2 in osteoblasts in the fracture callus. Therefore, our data indicate that Wnt1 boosts bone formation during fracture healing via YAP/BMP signaling both under healthy and osteoporotic conditions. To further test a potential translational application of Wnt1, we applied recombinant Wnt1 embedded into a collagen gel during critical-size bone-defect repair. Mice treated with Wnt1 displayed increased bone regeneration compared to control mice accompanied by increased YAP1/BMP2 expression in the defect area. These findings are of high clinical relevance because they indicate that Wnt1 could be used as a new therapeutic agent to treat orthopedic complications in the clinic.

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Section: Discussionmentioning

confidence: 99%

Wnt1 Boosts Fracture Healing by Enhancing Bone Formation in the Fracture Callus

Haffner‐Luntzer¹,

Ragipoglu²,

Ahmad³

et al. 2020

Journal of Bone and Mineral Research

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“…8 ). In cells possessing the Wnt signal, β-TRCP is released, as well as β-catenin and YAP/TAZ; YAP/TAZ and β-catenin can transfer into the nucleus to form YAP/TAZ-TEAD and β-catenin-TCF/LEF complexes, resulting in Wnt-induced transformation regeneration and ESC self-renewal ( 117 , 120 ). In addition, YAP/TAZ is the key downstream effector of alternative Wnt signaling to induce cell migration and osteogenic differentiation, as well as negative regulation of canonical Wnt/β-catenin signaling ( 119 ).…”

Section: Mechanism Of Yap/taz Regulationmentioning

confidence: 99%

Regulation and mechanism of YAP/TAZ in the mechanical microenvironment of stem cells (Review)

Wang

Zhong

2021

Mol Med Rep

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Stem cells receive cues from their physical and mechanical microenvironment via mechanosensing and mechanotransduction. These cues affect proliferation, self-renewal and differentiation into specific cell fates. A growing body of evidence suggests that yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) mechanotransduction is key for driving stem cell behavior and regeneration via the Hippo and other signaling pathways. YAP/TAZ receive a range of physical cues, including extracellular matrix stiffness, cell geometry, flow shear stress and mechanical forces in the cytoskeleton, and translate them into cell-specific transcriptional programs. However, the mechanism by which mechanical signals regulate YAP/TAZ activity in stem cells is not fully understand. The present review summarizes the current knowledge of the mechanisms involved in YAP/TAZ regulation on the physical and mechanical microenvironment, as well as its potential effects on stem cell differentiation. Contents 1. Introduction 2. Regulation of YAP/TAZ in mechanotransduction in stem cells 3. Mechanism of YAP/TAZ regulation 4. Conclusion

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“…In addition to the cross talk between the Hippo and Wnt/β-catenin signaling pathway, 74,85 the Hippo-YAP signaling pathway is critical for proper heart development. 87,88 Briefly, the Hippo signaling cascade involves sequential phosphorylation of the MST1/2 (mammalian STE20-like protein kinase 1/2)-SAV1 (salvador family protein 1) complex, which then phosphorylates the LATS1/2 (large tumor suppressor 1 and 2)-MOB1 (MPS one binder 1) complex (Figure 2).…”

Section: Cardiomyocyte Intrinsic Factors Involved In Pmdmentioning

confidence: 99%

Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering

Singh

Yücel

Garay

et al. 2023

Circulation Research

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During cardiac development and morphogenesis, cardiac progenitor cells differentiate into cardiomyocytes that expand in number and size to generate the fully formed heart. Much is known about the factors that regulate initial differentiation of cardiomyocytes, and there is ongoing research to identify how these fetal and immature cardiomyocytes develop into fully functioning, mature cells. Accumulating evidence indicates that maturation limits proliferation and conversely proliferation occurs rarely in cardiomyocytes of the adult myocardium. We term this oppositional interplay the proliferation-maturation dichotomy. Here we review the factors that are involved in this interplay and discuss how a better understanding of the proliferation-maturation dichotomy could advance the utility of human induced pluripotent stem cell–derived cardiomyocytes for modeling in 3-dimensional engineered cardiac tissues to obtain truly adult-level function.

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Role of Hippo-YAP1/TAZ pathway and its crosstalk in cardiac biology

Cited by 18 publications

References 98 publications

Wnt1 Boosts Fracture Healing by Enhancing Bone Formation in the Fracture Callus

Wnt1 Boosts Fracture Healing by Enhancing Bone Formation in the Fracture Callus

Regulation and mechanism of YAP/TAZ in the mechanical microenvironment of stem cells (Review)

Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering

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