Comparative proteomics analysis ofmyocardium inmouse model
of diabetic cardiomyopathy using the iTRAQ technique

Shao, Mingfeng; Chen, Jing; Zheng, Shaojiang

doi:10.17219/acem/74539

Cited by 4 publications

(4 citation statements)

References 39 publications

(42 reference statements)

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“…Our interrogation of independent RNA expression data and western blot data shows consistent upregulation in Sorbs2 across a range of myocardial diseases, as has been recently noted. 73 Further, Sorbs2 protein is upregulated in LVNC, 8 diabetic cardiomyopathy, 6 and is released from infarcted myocardium. 4 Upregulation is potentially mediated by Mef2 transcription factors, 74 although posttranscriptional regulation by disease-relevant microRNAs and RNA-binding proteins may also contribute.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Prior reports indicate that Sorbs2 expression is altered in the setting of myocardial infarction and diabetic cardiomyopathy, and its suppression in vitro induces cardiomyocyte hypertrophy. [4][5][6] In addition, recent in vivo studies suggest both pathogenic and protective roles for Sorbs2 in the development of arrhythmogenic right ventricular cardiomyopathy (ARVC) 7 and left ventricular non-compaction (LVNC). 8 Specifically, Ding et al reported that global Sorbs2 knockout mice (KO) develop lethal ARVC with severe right ventricle (RV) failure at 4-6 months of age.…”

Section: Introductionmentioning

confidence: 99%

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Knockout of Sorbs2 in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice

McLendon

Zhang

Matasic

et al. 2022

Preprint

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Rationale: Sorbs2 is a cardiomyocyte-enriched, cytoskeletal adaptor protein, and given some evidence for its dysregulated expression in failing hearts, there is growing interest in understanding its roles in cardiac biology and disease. While Sorbs2 global knockout mice display lethal cardiomyopathy with severe arrhythmias, the underlying mechanisms remain unclear, and whether this results from intrinsic loss of Sorbs2 in cardiomyocytes is unknown, as Sorbs2 is also well-expressed in the nervous system and vasculature. In addition, the potential relevance of Sorbs2 in human cardiomyopathy remains underexplored. Objective: To characterize the effects and potential underlying mechanisms of cardiomyocyte-specific deletion of Sorbs2 on cardiac structure and function in mice, and to further examine Sorbs2 dysregulation in failing hearts and explore potential links between Sorbs2 genetic variations and human cardiovascular disease phenotypes. Methods and Results: We report that myocardial Sorbs2 expression is consistently upregulated in humans with ischemic and idiopathic cardiomyopathies, and in experimental animal models of heart failure (HF). We generated mice with cardiomyocyte-specific loss of Sorbs2 (Sorbs2-cKO) and found early atrial and ventricular conduction abnormalities, despite unaltered expression of primary action potential ion channels and gap junction proteins. At mid-life, Sorbs2-cKO mice exhibit impaired cardiac contractility with cardiomyofibers failing to maintain adequate mechanical tension. As a result, these mice develop progressive diastolic and systolic dysfunction, enlarged cardiac chambers, and die with congestive HF at approximately one year of age. Comprehensive survey of potential underlying mechanisms revealed that Sorbs2-cKO hearts exhibit defective microtubule polymerization and compensatory upregulation of structural proteins desmin, vinculin, and tubulins. Finally, consistent with our observations in mice, we identified suggestive links between Sorbs2 genetic variants and related human cardiac phenotypes, including conduction abnormalities, atrial enlargement, and dilated cardiomyopathy. Conclusions: Our studies show that Sorbs2 is essential for maintaining cytoskeletal structural integrity in cardiomyocytes likely through strengthening the interactions between microtubules and other structural proteins at crosslink sites. Overall, this study provides key insights into the critical role for Sorbs2 in cardiomyocytes and likely other cell types in maintaining normal cardiac structure and function and highlights its potential clinical relevance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Knockout of Sorbs2 in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice

McLendon

Zhang

Matasic

et al. 2022

Preprint

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“…SORBS2 was closely related to cell adhesion, and it localized in actin stress fibers [ 32 ]. Proteomics analysis presented that SORBS2 was obviously upregulated in the diabetic cardiomyopathy model [ 33 ]. And another study suggested SORBS2 involved in DN progression through regulating actin filaments [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy

Ran

Zhu

Zhong

et al. 2020

Diabetol Metab Syndr

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Background It has been reported that long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). Our study aims to research the function of lncRNA KCNQ1OT1 in DN cells and the molecular mechanism. Methods Human glomerular mesangial cells (HGMCs) and human renal glomerular endothelial cells (HRGECs) were cultured in high glucose (30 mM) condition as models of DN cells. KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and miR-18b-5p levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mRNA and protein levels of Sorbin and SH3 domain-containing protein 2 (SORBS2), Type IV collagen (Col-4), fibronectin (FN), transcriptional regulatory factor-beta 1 (TGF-β1), Twist, NF-κB and STAT3 were measured by qRT-PCR and western blot. Cell viability was detected by cell counting kit-8 (CCK-8) assay for selecting the proper concentration of glucose treatment. Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry assay were employed to determine cell proliferation and apoptosis, respectively. The targets of KCNQ1OT1 was predicted by online software and confirmed by dual-luciferase reporter assay. Results KCNQ1OT1 and SORBS2 were elevated in DN. Both knockdown of KCNQ1OT1 and silencing of SORBS2 restrained proliferation and fibrosis and induced apoptosis in DN cells. Besides, Overexpression of SORBS2 restored the KCNQ1OT1 knockdown-mediate effects on proliferation, apoptosis and fibrosis in DN cells. In addition, miR-18b-5p served as a target of KCNQ1OT1 as well as targeted SORBS2. KCNQ1OT1 knockdown repressed NF-ĸB pathway. Conclusion KCNQ1OT1 regulated DN cells proliferation, apoptosis and fibrosis via KCNQ1OT1/miR-18b-5p/SORBS2 axis and NF-ĸB pathway.

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“…Previous research using proteomic analysis of myocardial tissue has identified new pathophysiological mechanisms contributing to cardiovascular diseases such as ischemic cardiomyopathy [ 15 ], dilated cardiomyopathy (DCM) [ 14 ], diabetic cardiomyopathy [ 17 , 18 ], and atherosclerosis [ 19 ]. Recently, we showed changes in platelet proteins, such as clusterin, CXC-motif-chemokine, cathepsin, creatine-kinase-B and myotrophin, to be associated with cellular, biologic, metabolic, immune, and coagulation system processes involved in the development of CHF caused by MMVD in dogs [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Proteomic Changes in Dogs with Different Stages of Chronic Heart Failure

Sarıl

Kocatürk

Shimada

et al. 2022

Animals

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MMVD, the most common cause of CHF in dogs, is a chronic disease with variable clinical signs, with some patients remaining asymptomatic while others develop CHF. Here, we aimed to evaluate serum proteins by proteomic analysis in dogs at different stages of CHF due to MMVD, and proteome behaviors after conventional treatment. A total of 32 dogs were divided equally into four groups—stage A (healthy/controls), stage B2 (asymptomatic), stage C and stage D (symptomatic)—according to the ACVIM consensus. Serum proteomes were evaluated using LC/MS-based label-free differential proteome analysis. The study revealed 157 different proteins; 11 were up- and 21 down-regulated in dogs with CHF compared to controls. In stage B2 dogs, angiotensinogen (AGT) was up-regulated, but immunoglobulin iota chain-like, lipopolysaccharide-binding protein, and carboxypeptidase (CPN) were down-regulated. In stage C dogs, complement C3 (C3) and inter-alpha-trypsin inhibitor heavy chain were up-regulated, but hemopexin, and actin-cytoplasmic-1 (ACT-1) were down-regulated. In stage D dogs, AGT was up-regulated, whereas tetranectin, paraoxonase-1, adiponectin and ACT-1 were down-regulated. A decrease in CPN, C3 and AGT and an increase in ACT-1 were observed after treatment of dogs in stage C. This pilot study identified that dogs at different stages of CHF show different serum protein composition which has potential to be biomarker for diagnose and treatment monitorization.

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Comparative proteomics analysis ofmyocardium inmouse model of diabetic cardiomyopathy using the iTRAQ technique

Abstract: These results suggest that DCM shows differences in its proteomics compared to normal controls. Our quantitative proteomic analysis may provide a new insight into the distinct molecular profile of DCM.

Cited by 4 publications

References 39 publications

Knockout of Sorbs2 in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice

Knockout of Sorbs2 in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice

LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy

Serum Proteomic Changes in Dogs with Different Stages of Chronic Heart Failure

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