Polydatin attenuates tubulointerstitial fibrosis in diabetic kidney disease by inhibiting YAP expression and nuclear translocation

He, Manlin; Feng, Lan; Chen, Yang; Gao, Bin; Du, Yiwei; Zhou, Lu; Li, Fēi; Liu, Hongbao

doi:10.3389/fphys.2022.927794

Cited by 5 publications

(5 citation statements)

References 67 publications

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“…Polydatin (PD) is a natural active ingredient in the thuja family of plants. A study demonstrated that the mechanism of PD inhibiting YAP activity and nuclear translocation is similar to VP, but its function in reducing α‐SMA expression and collagen I deposition was more pronounced compared with VP 310 . In the activated Hippo signaling pathway 14‐3‐3ζ can bind to YAP/TAZ in the cytoplasm and contributes to YAP/TAZ degradation.…”

Section: Yap/taz and Fibrosismentioning

confidence: 99%

“…A study demonstrated that the mechanism of PD inhibiting YAP activity and nuclear translocation is similar to VP, but its function in reducing α‐SMA expression and collagen I deposition was more pronounced compared with VP. 310 In the activated Hippo signaling pathway 14‐3‐3ζ can bind to YAP/TAZ in the cytoplasm and contributes to YAP/TAZ degradation. It was found that when in a mouse model of acute kidney injury with 14‐3‐3ζ overexpression, the expression of fibrosis‐related proteins was downregulated and interstitial fibrosis was alleviated.…”

Section: Yap/taz and Fibrosismentioning

confidence: 99%

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YAP/TAZ: Molecular pathway and disease therapy

Wei,

Hui,

Chen

et al. 2023

MedComm

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The Yes‐associated protein and its transcriptional coactivator with PDZ‐binding motif (YAP/TAZ) are two homologous transcriptional coactivators that lie at the center of a key regulatory network of Hippo, Wnt, GPCR, estrogen, mechanical, and metabolism signaling. YAP/TAZ influences the expressions of downstream genes and proteins as well as enzyme activity in metabolic cycles, cell proliferation, inflammatory factor expression, and the transdifferentiation of fibroblasts into myofibroblasts. YAP/TAZ can also be regulated through epigenetic regulation and posttranslational modifications. Consequently, the regulatory function of these mechanisms implicates YAP/TAZ in the pathogenesis of metabolism‐related diseases, atherosclerosis, fibrosis, and the delicate equilibrium between cancer progression and organ regeneration. As such, there arises a pressing need for thorough investigation of YAP/TAZ in clinical settings. In this paper, we aim to elucidate the signaling pathways that regulate YAP/TAZ and explore the mechanisms of YAP/TAZ‐induce diseases and their potential therapeutic interventions. Furthermore, we summarize the current clinical studies investigating treatments targeting YAP/TAZ. We also address the limitations of existing research on YAP/TAZ and propose future directions for research. In conclusion, this review aims to provide fresh insights into the signaling mediated by YAP/TAZ and identify potential therapeutic targets to present innovative solutions to overcome the challenges associated with YAP/TAZ.

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Section: Yap/taz and Fibrosismentioning

confidence: 99%

Section: Yap/taz and Fibrosismentioning

confidence: 99%

YAP/TAZ: Molecular pathway and disease therapy

Wei,

Hui,

Chen

et al. 2023

MedComm

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“…To assess the suggested model's performance on bigger and more varied datasets, more investigation is required. Chen et al used a convolutional neural network (CNN) model to apply deep learning to the detection of CKD [4]. On a benchmark dataset, the suggested CNN model produced cutting-edge results, showcasing the potential of deep learning for CKD detection.…”

Section: Related Workmentioning

confidence: 99%

Predictive Modeling of Chronic Kidney Disease: An Ensemble ML Approach

et al. 2023

IJFMR

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Globally, Chronic kidney disease (CKD) is becoming a significant threat to public health, As Effective management and treatment of CKD depend heavily on early detection. In this study, we propose an in depth approach for CKD detection through stacking of machine learning. We utilized a hospital dataset with 25 features to develop prediction models for the classification of chronic kidney disease. The dataset is intended for a classification challenge and contains multivariate data. After that, the data was divided into training and testing sets using an 80-20 split, making it possible to assess the performance of the model. Many machine learning models were used, however one stacked model that included the Random Forest Classifier, Gradient Boosting Machine (RG), Convolutional Neural Network (CNN), and Decision Tree received special attention. The suitability of these models for the CKD classification assignment led to their selection. After hyperparameter tuning was done to maximize the models' performance, the models were assessed using metrics including AUC, accuracy, F1 score, precision, and recall on the testing dataset. Our research showed that the layered RG model produced very good outcomes. Later, hyperparameter tuning was done to maximize the models' performance, the models were assessed using metrics including AUC, accuracy, F1 score, precision, and recall on the testing dataset. Our results showed that the layered RG model produced very good outcomes. These results demonstrate how machine learning can be used to diagnose chronic kidney disease (CKD) early and have positive effects on healthcare by providing a way to improve patient outcomes and healthcare management.

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“… 11 In the Hippo pathway, LATS1 and MST1 are protein kinases which, on activation, stimulate LATS1 phosphorylation of important downstream effectors such as TAZ and YAP. 12 In particular, as a key factor in the pathway, YAP controls the size of organs by mediating epithelial–mesenchymal transformation and regulating cell contact inhibition as well as cell apoptosis, differentiation, and proliferation. It has been previously shown that targeting the activation of YAP in human cancer was of interest for the development of chemotherapeutic drugs.…”

Section: Introduction To the Hippo/yap Pathwaymentioning

confidence: 99%

“…Moreover, YAP’s functions in diabetic vascular ECs were also explored, with results showing that inhibiting YAP decreased tube formation, cell proliferation, and cell migration under hypoxic conditions. 12 , 17 Therefore, YAP is a key regulator of tumor growth and invasion while being an important link in glucose metabolism as its activation regulates gluconeogenesis and hence glucose tolerance levels. 27 The localization of YAP, which is the nuclear sensor of the Hippo pathway, is indicative of the activation state of the Takeda G-coupled receptor 5 (TGR5), and as such, YAP is important to determine the intestinal structure as well as the fate of different cells, particularly during epithelial regeneration.…”

Section: Introduction To the Hippo/yap Pathwaymentioning

confidence: 99%

Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications

Wei,

Gao,

Wang

et al. 2023

Therapeutic Advances in Endocrinology

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Diabetic angiopathy, which includes diabetic kidney disease (DKD), cardio-cerebrovascular disease, and diabetic retinopathy (DR) among other diseases, is one of the most common complications affecting diabetic patients. Among these, DKD, which is a major cause of morbidity and mortality, affects about 40% of diabetic patients. Similarly, DR involves retinal neovascularization and neurodegeneration as a result of chronic hyperglycemia and is the main cause of visual impairment and blindness. In addition, inflammation also promotes atherosclerosis and diabetes, with atherosclerosis-related cardiovascular diseases being often a main cause of disability or death in diabetic patients. Given that vascular diseases caused by diabetes negatively impact human health, it is therefore important to identify appropriate treatments. In this context, some studies have found that the Hippo/Yes-associated protein (YAP) pathway is a highly evolutionarily conserved protein kinase signal pathway that regulates organ growth and size through its effector signaling pathway Transcriptional co-Activator with PDZ-binding motif (TAZ) and its YAP. YAP is a key factor in the Hippo pathway. The activation of YAP regulates gluconeogenesis, thereby regulating glucose tolerance levels; silencing the YAP gene thereby prevents the formation of glomerular fibrosis. YAP can combine with TEA domain family members to regulate the proliferation and migration of retinal vascular endothelial cells (ECs), so YAP plays a prominent role in the formation and pathology of retinal vessels. In addition, YAP/TAZ activation and translocation to the nucleus promote endothelial inflammation and monocyte-EC attachment, which can increase diabetes-induced cardiovascular atherosclerosis. Hippo/YAP signaling pathway provides a potential therapeutic target for diabetic angiopathy, which can prevent the progression of diabetes to DR and improve renal fibrosis and cardio-vascular atherosclerosis.

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Polydatin attenuates tubulointerstitial fibrosis in diabetic kidney disease by inhibiting YAP expression and nuclear translocation

Cited by 5 publications

References 67 publications

YAP/TAZ: Molecular pathway and disease therapy

YAP/TAZ: Molecular pathway and disease therapy

Predictive Modeling of Chronic Kidney Disease: An Ensemble ML Approach

Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications

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