Context-dependent transcriptional regulations of YAP/TAZ in stem cell and differentiation

Luo, Juan; Li, Peng

doi:10.1186/s13287-021-02686-y

Cited by 30 publications

(27 citation statements)

References 89 publications

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“…Numerous evidence suggests that these components, especially YAP, have a key role in organ development and tissue homeostasis via regulation of cellular behaviors such as cell proliferation, survival, apoptosis, migration and differentiation [ 10 ]. Hippo signaling also controls stem cells self-renewal, proliferation and differentiation [ 11 ], triggering the regeneration of tissue [ 12 ]. Upon activation, MST1/2 kinase undergoes autophosphorylation and activates LATS1/2 and MOB1.…”

Section: Introductionmentioning

confidence: 99%

Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Zhou¹,

Lei²,

Yang³

et al. 2023

IJMS

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Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the occurrence of cognitive deficits. With no effective treatments available, the search for new effective therapies has become a major focus of interest. In the present study, we describe the potential therapeutic effect of Artemisia annua (A. annua) extract on AD. Nine-month-old female 3xTg AD mice were treated with A. annua extract for three months via oral administration. Animals assigned to WT and model groups were administrated with an equal volume of water for the same period. Treated AD mice significantly improved the cognitive deficits and exhibited reduced Aβ accumulation, hyper-phosphorylation of tau, inflammatory factor release and apoptosis when compared with untreated AD mice. Moreover, A. annua extract promoted the survival and proliferation of neural progenitor cells (NPS) and increased the expression of synaptic proteins. Further assessment of the implicated mechanisms revealed that A. annua extract regulates the YAP signaling pathway in 3xTg AD mice. Further studies comprised the incubation of PC12 cells with Aβ1–42 at a concentration of 8 μM with or without different concentrations of A. annua extract for 24 h. Obtained ROS levels, mitochondrial membrane potential, caspase-3 activity, neuronal cell apoptosis and assessment of the signaling pathways involved was performed using western blot and immunofluorescence staining. The obtained results showed that A. annua extract significantly reversed the Aβ1–42-induced increase in ROS levels, caspase-3 activity and neuronal cell apoptosis in vitro. Moreover, either inhibition of the YAP signaling pathway, using a specific inhibitor or CRISPR cas9 knockout of YAP gene, reduced the neuroprotective effect of the A. annua extract. These findings suggest that A. annua extract may be a new multi-target anti-AD drug with potential use in the prevention and treatment of AD.

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Section: Introductionmentioning

confidence: 99%

Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Zhou¹,

Lei²,

Yang³

et al. 2023

IJMS

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“…These crosslinks are characteristic of mature cartilage. This is significant as cell processes, particularly in tissue engineering, are often context dependent [52][53][54] . It is interesting to note that condition 25 at 1/15 th was optimal for type II collagen expression as compared to condition 25 at 1x, as seen by luminescence, immunofluorescence and western blot.…”

Section: These Findings Relied On the Use Of Response Surface Methodo...mentioning

confidence: 99%

Micronutrient Optimization Using Design of Experiments Approach in Tissue Engineered Articular Cartilage for Production of Type II Collagen

Cruz

Gonzalez

Toro

et al. 2022

Preprint

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Tissue Engineering of cartilage has been hampered by the inability of engineered tissue to express native levels of type II collagen in vitro. Inadequate levels of type II collagen are, in part, due to a failure to recapitulate the physiological environment in culture. In this study, we engineered primary rabbit chondrocytes to express a secreted reporter, Gaussia Luciferase, driven by the type II collagen promoter, and applied a Design of Experiments approach to assess chondrogenic differentiation in micronutrient-supplemented medium. Using a Response Surface Model, 240 combinations of micronutrients absent in standard chondrogenic differentiation medium, were screened and assessed for type II collagen expression. Five conditions predicted to produce the greatest Luciferase expression were selected for further study. Validation of these conditions in 3D aggregates identified an optimal condition for type II collagen expression. Engineered cartilage grown in this condition, showed a 170% increase in type II collagen expression (Day 22 Luminescence) and in Youngs tensile modulus compared to engineered cartilage in basal media alone. Collagen cross-linking analysis confirmed formation of type II-type : II collagen and type II-type : IX collagen cross-linked heteropolymeric fibrils, characteristic of mature native cartilage. Combining a Design of Experiments approach and secreted reporter cells in 3D aggregate culture enabled a high-throughput platform that can be used to identify more optimal physiological culture parameters for chondrogenesis.

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“…Concerning this signaling pathway role in CNS homeostasis and pathology, it controls the balance between cell proliferation and apoptosis and is implied in the regulation of the volume of injured tissues. Specifically, YAP/TAZ has been shown to regulate the proliferation, differentiation and apoptosis of NSC ( Luo and Li, 2022 ). In glioblastoma, the tumor nature of proliferative cells implies an upregulation of the YAP/TAZ signaling pathway ( Jin et al, 2020 ).…”

Section: The Extracellular Matrix Role In the Process Of Mechanotrans...mentioning

confidence: 99%

Mechanotransduction: Exploring New Therapeutic Avenues in Central Nervous System Pathology

et al. 2022

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Cells are continuously exposed to physical forces and the central nervous system (CNS) is no exception. Cells dynamically adapt their behavior and remodel the surrounding environment in response to forces. The importance of mechanotransduction in the CNS is illustrated by exploring its role in CNS pathology development and progression. The crosstalk between the biochemical and biophysical components of the extracellular matrix (ECM) are here described, considering the recent explosion of literature demonstrating the powerful influence of biophysical stimuli like density, rigidity and geometry of the ECM on cell behavior. This review aims at integrating mechanical properties into our understanding of the molecular basis of CNS disease. The mechanisms that mediate mechanotransduction events, like integrin, Rho/ROCK and matrix metalloproteinases signaling pathways are revised. Analysis of CNS pathologies in this context has revealed that a wide range of neurological diseases share as hallmarks alterations of the tissue mechanical properties. Therefore, it is our belief that the understanding of CNS mechanotransduction pathways may lead to the development of improved medical devices and diagnostic methods as well as new therapeutic targets and strategies for CNS repair.

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Context-dependent transcriptional regulations of YAP/TAZ in stem cell and differentiation

Cited by 30 publications

References 89 publications

Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer’s Disease via Regulating YAP Signaling

Micronutrient Optimization Using Design of Experiments Approach in Tissue Engineered Articular Cartilage for Production of Type II Collagen

Mechanotransduction: Exploring New Therapeutic Avenues in Central Nervous System Pathology

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