The Role of Oxidative Inactivation of Phosphatase PTEN and TCPTP in Fatty Liver Disease

Huu, Thang Nguyen; Park, Jiyoung; Zhang, Ying; Thanh, Hien Duong; Park, Iha; Choi, Jin Kyeong; Yoon, Hyun Joong; Park, Sang Chul; Woo, Hyun Ae; Lee, Seung-Rock

doi:10.3390/antiox12010120

Cited by 7 publications

(4 citation statements)

References 132 publications

(203 reference statements)

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“…Notably, JUN, TLR4, and ANXA5, like ANXA2, showed a trend of upregulation with increasing NAFLD in our three datasets. JUN, TLR4 ( 42 ), EGFR ( 43 ), and TNF ( 44 ) were confirmed to promote the progression of NAFLD in previous studies, while ANXA5 ( 45 ) and PTEN ( 46 ) were identified as protective factors. TP53 has a dual role in NAFLD ( 47 ).…”

Section: Discussionmentioning

confidence: 54%

Machine learning identifies ferroptosis-related gene ANXA2 as potential diagnostic biomarkers for NAFLD

Qin,

Cao,

Ding

et al. 2023

Front. Endocrinol.

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IntroductionNon-alcoholic fatty liver disease (NAFLD), a major cause of chronic liver disease, still lacks effective therapeutic targets today. Ferroptosis, a type of cell death characterized by lipid peroxidation, has been linked to NAFLD in certain preclinical trials, yet the exact molecular mechanism remains unclear. Thus, we analyzed the relationship between ferroptosis genes and NAFLD using high-throughput data.MethodWe utilized a total of 282 samples from five datasets, including two mouse ones, one human one, one single nucleus dataset and one single cell dataset from Gene Expression Omnibus (GEO), as the data basis of our study. To filter robust treatment targets, we employed four machine learning methods (LASSO, SVM, RF and Boruta). In addition, we used an unsupervised consensus clustering algorithm to establish a typing scheme for NAFLD based on the expression of ferroptosis related genes (FRGs). Our study is also the first to investigate the dynamics of FRGs throughout the disease process by time series analysis. Finally, we validated the relationship between core gene and ferroptosis by in vitro experiments on HepG2 cells.ResultsWe discovered ANXA2 as a central focus in NAFLD and indicated its potential to boost ferroptosis in HepG2 cells. Additionally, based on the results obtained from time series analysis, ANXA2 was observed to significantly define the disease course of NAFLD. Our results demonstrate that implementing a ferroptosis-based staging method may hold promise for the diagnosis and treatment of NAFLD.ConclusionOur findings suggest that ANXA2 may be a useful biomarker for the diagnosis and characterization of NAFLD.

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Section: Discussionmentioning

confidence: 54%

Machine learning identifies ferroptosis-related gene ANXA2 as potential diagnostic biomarkers for NAFLD

Qin,

Cao,

Ding

et al. 2023

Front. Endocrinol.

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“…Moreover, the migration of HSCs is affected by EC-derived EVs containing sphingosine kinase 1 (SK1), which mediates HSC chemotaxis through the SK1-S1P pathway ( 49 ). Besides, Studies have reported that PTEN has been proved to play an important role in the fibrosis in kidney ( 106 ) and liver ( 107 ) and highly related to exosome. For example, lipotoxic hepatocytes exosome transplantation aggravated the degree of PTEN-induced expression of putative protein kinase 1 (PINK1) mediated mitophagy suppression, steatohepatitis, lipidosis, and fibrosis in the livers of NAFLD mice with cirrhosis ( 108 ).…”

Section: The Role Of Evs In Nafldmentioning

confidence: 99%

Role of extracellular vesicles in nonalcoholic fatty liver disease

et al. 2023

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BackgroundNonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that affects approximately one-quarter of the global population and is becoming increasingly prevalent worldwide. The lack of current noninvasive tools and efficient treatment is recognized as a significant barrier to the clinical management of these conditions. Extracellular vesicles (EVs) are nanoscale vesicles released by various cells and deliver bioactive molecules to target cells, thereby mediating various processes, including the development of NAFLD.Scope of reviewThere is still a long way to actualize the application of EVs in NAFLD diagnosis and treatment. Herein, we summarize the roles of EVs in NAFLD and highlight their prospects for clinical application as a novel noninvasive diagnostic tool as well as a promising therapy for NAFLD, owing to their unique physiochemical characteristics. We summarize the literatures on the mechanisms by which EVs act as mediators of intercellular communication by regulating metabolism, insulin resistance, inflammation, immune response, intestinal microecology, and fibrosis in NAFLD. We also discuss future challenges that must be resolved to improve the therapeutic potential of EVs.Major conclusionsThe levels and contents of EVs change dynamically at different stages of diseases and this phenomenon may be exploited for establishing sensitive stage-specific markers. EVs also have high application potential as drug delivery systems with low immunogenicity and high biocompatibility and can be easily engineered. Research on the mechanisms and clinical applications of EVs in NAFLD is in its initial phase and the applicability of EVs in NAFLD diagnosis and treatment is expected to grow with technological progress.

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“…MC activation comes with ROS production; ROS regulate various signaling pathways, thus providing the release of inflammatory mediators and various cytokine production. Protein tyrosine phosphatases (PTPs) are a superfamily of enzymes that are the main targets for ROS due to an oxidation-susceptible nucleophilic cysteine at their active site [ 119 ]. As reported, direct and indirect regulations of class I and II Cys-based protein tyrosine phosphatases (PTEN, LMW-PTP, SHP-2, PTP-PEST, PTP1B, DEP-1, TC45, LAR, etc.)…”

Section: Reactive Oxygen Species In the Mechanisms Of Activation Of M...mentioning

confidence: 99%

Mast Cells as a Potential Target of Molecular Hydrogen in Regulating the Local Tissue Microenvironment

et al. 2023

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Knowledge of the biological effects of molecular hydrogen (H2), hydrogen gas, is constantly advancing, giving a reason for the optimism in several healthcare practitioners regarding the management of multiple diseases, including socially significant ones (malignant neoplasms, diabetes mellitus, viral hepatitis, mental and behavioral disorders). However, mechanisms underlying the biological effects of H2 are still being actively debated. In this review, we focus on mast cells as a potential target for H2 at the specific tissue microenvironment level. H2 regulates the processing of pro-inflammatory components of the mast cell secretome and their entry into the extracellular matrix; this can significantly affect the capacity of the integrated-buffer metabolism and the structure of the immune landscape of the local tissue microenvironment. The analysis performed highlights several potential mechanisms for developing the biological effects of H2 and offers great opportunities for translating the obtained findings into clinical practice.

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The Role of Oxidative Inactivation of Phosphatase PTEN and TCPTP in Fatty Liver Disease

Cited by 7 publications

References 132 publications

Machine learning identifies ferroptosis-related gene ANXA2 as potential diagnostic biomarkers for NAFLD

Machine learning identifies ferroptosis-related gene ANXA2 as potential diagnostic biomarkers for NAFLD

Role of extracellular vesicles in nonalcoholic fatty liver disease

Mast Cells as a Potential Target of Molecular Hydrogen in Regulating the Local Tissue Microenvironment

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