Role of Moesin Phosphorylation in Retinal Pericyte Migration and Detachment Induced by Advanced Glycation Endproducts

Zhang, Shuang-Shuang; Hu, Jiaqing; Liu, Xiaohui; Chen, Lixian; Guo, Xiaohua; Huang, Qiaobing

doi:10.3389/fendo.2020.603450

Cited by 15 publications

(8 citation statements)

References 71 publications

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“…Zhang et al. have shown that the interaction of CD44 with phosphorylated moesin leads to less pericyte coverage and disruption of vessel integrity, which may contribute to neovascularization in DR ( 48 ). NOX4 is a member of the NADPH oxidase family of enzymes, which catalyze the reduction of molecular oxygen to various reactive oxygen species ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential ferroptosis-related biomarkers and a pharmacological compound in diabetic retinopathy based on machine learning and molecular docking

Liu

Cheng

et al. 2022

Front. Endocrinol.

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BackgroundDiabetic retinopathy (DR), a neurovascular disease, is a leading cause of visual loss worldwide and severely affects quality of life. Several studies have shown that ferroptosis plays an important role in the pathogenesis of DR; however, its molecule mechanism remains incompletely elucidated. Hence, this study aimed to investigate the pathogenesis of ferroptosis and explore potential ferroptosis-related gene biomarkers and a pharmacological compound for treating DR.MethodsFerroptosis-related differentially expressed genes (DEGs) were identified in the GSE102485 dataset. Functional enrichment analyses were then performed and a protein-protein interaction (PPI) network was constructed to screen candidates of ferroptosis-related hub genes (FRHGs). FRHGs were further screened based on least absolute shrinkage and selection operator (LASSO) regression and random forest algorithms, and were then validated with the GSE60436 dataset and previous studies. A receiver operating characteristic (ROC) curve monofactor analysis was conducted to evaluate the diagnostic performance of the FRHGs, and immune infiltration analysis was performed. Moreover, the pharmacological compound targeting the FRHGs were verified by molecular docking. Finally, the FRHGs were validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis.ResultsThe 40 ferroptosis-related DEGs were extracted, and functional enrichment analyses mainly implicated apoptotic signaling, response to oxidative stress, ferroptosis, and lipid and atherosclerosis pathways. By integrating the PPI, LASSO regression, and random forest analyses to screen the FRHGs, and through validation, we identified five FRHGs that performed well in the diagnosis (CAV1, CD44, NOX4, TLR4, and TP53). Immune infiltration analysis revealed that immune microenvironment changes in DR patients may be related to these five FRHGs. Molecular docking also showed that glutathione strongly bound the CAV1 and TLR4 proteins. Finally, the upregulated expression of FRHGs (CD44, NOX4, TLR4, and TP53) was validated by qRT-PCR analysis in human retinal capillary endothelial cells cultured under high-glucose environment.ConclusionsCAV1, CD44, NOX4, TLR4, and TP53 are potential biomarkers for DR and may be involved in its occurrence and progression by regulating ferroptosis and the immune microenvironment. Further, glutathione exhibits potential therapeutic efficacy on DR by targeting ferroptosis. Our study provides new insights into the ferroptosis-related pathogenesis of DR, as well as its diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Identification of potential ferroptosis-related biomarkers and a pharmacological compound in diabetic retinopathy based on machine learning and molecular docking

Liu

Cheng

et al. 2022

Front. Endocrinol.

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“…Pericyte detachment is a key mechanism underlying bridge cell and basement membrane bridge formation and is an essential factor that accelerates DR progression, further destabilizing retinal vascular endothelial cells ( Park et al, 2017 ; Corliss et al, 2020 ). AGEs can activate Rho-kinase to mediate moesin phosphorylation at Thr558, and the resulting phospho-moesin interacts with CD44 to form the CD44 cluster, which may stimulate the migration of pericytes and subsequent pericyte detachment in microvessels ( Zhang S. S. et al, 2020 ).…”

Section: Involved Cellsmentioning

confidence: 99%

Diabetic retinopathy: Involved cells, biomarkers, and treatments

et al. 2022

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Diabetic retinopathy (DR), a leading cause of vision loss and blindness worldwide, is caused by retinal neurovascular unit dysfunction, and its cellular pathology involves at least nine kinds of retinal cells, including photoreceptors, horizontal and bipolar cells, amacrine cells, retinal ganglion cells, glial cells (Müller cells, astrocytes, and microglia), endothelial cells, pericytes, and retinal pigment epithelial cells. Its mechanism is complicated and involves loss of cells, inflammatory factor production, neovascularization, and BRB impairment. However, the mechanism has not been completely elucidated. Drug treatment for DR has been gradually advancing recently. Research on potential drug targets relies upon clear information on pathogenesis and effective biomarkers. Therefore, we reviewed the recent literature on the cellular pathology and the diagnostic and prognostic biomarkers of DR in terms of blood, protein, and clinical and preclinical drug therapy (including synthesized molecules and natural molecules). This review may provide a theoretical basis for further DR research.

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“…CD44 is believed to be involved in tumour growth and metastasis, proliferative diabetic retinopathy and atherosclerosis [ 45 ]. In a recent study, AGEs (Advanced Glycation Endproducts) were found to interact with CD44 to form stress fibres and RMP (Retinal Microvascular Pericytes) migration, causing pericytes to detach from microvessels and damage vascular integrity [ 46 ]. Moreover, activation of the CD44 receptor signalling pathway may result in the release of multiple inflammatory factors, while up-regulation of ICAM-1 indirectly leads to increased endothelial cell activation [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

The integrated transcriptome bioinformatics analysis identifies key genes and cellular components for proliferative diabetic retinopathy

et al. 2022

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Proliferative Diabetic Retinopathy (PDR) is a chronic complication of Diabetes and the main cause of blindness among the world’s working population at present. While there have been many studies on the pathogenesis of PDR, its intrinsic molecular mechanisms have not yet been fully elucidated. In recent years, several studies have employed bulk RNA-sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) to profile differentially expressed genes (DEGs) and cellular components associated with PDR. This study adds to this expanding body of work by identifying PDR’s target genes and cellular components by conducting an integrated transcriptome bioinformatics analysis. This study integrately examined two public bulk RNA-seq datasets(including 11 PDR patients and 7 controls) and one single-cell RNA-seq datasets(including 5 PDR patients) of Fibro (Vascular) Membranes (FVMs) from PDR patients and control. A total of 176 genes were identified as DEGs between PDR patients and control among both bulk RNA-seq datasets. Based on these DEGs, 14 proteins were identified in the protein overlap within the significant ligand-receptor interactions of retinal FVMs and Protein-Protein Interaction (PPI) network, three of which were associated with PDR (CD44, ICAM1, POSTN), and POSTN might act as key ligand. This finding may provide novel gene signatures and therapeutic targets for PDR.

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Role of Moesin Phosphorylation in Retinal Pericyte Migration and Detachment Induced by Advanced Glycation Endproducts

Cited by 15 publications

References 71 publications

Identification of potential ferroptosis-related biomarkers and a pharmacological compound in diabetic retinopathy based on machine learning and molecular docking

Identification of potential ferroptosis-related biomarkers and a pharmacological compound in diabetic retinopathy based on machine learning and molecular docking

Diabetic retinopathy: Involved cells, biomarkers, and treatments

The integrated transcriptome bioinformatics analysis identifies key genes and cellular components for proliferative diabetic retinopathy

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