WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy

Hashemi, Ehsan; Dehghanbanadaki, Hojat; Baharanchi, Alireza Abbasi; Forouzanfar, Katayoon; Kakaei, Ardeshir; Mohammadi, Seyed Mohammad; Zeidi, Saba; Razi, Farideh

doi:10.1186/s12967-021-02964-6

Cited by 10 publications

(5 citation statements)

References 39 publications

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“…However, recent quantitative RNA sequencing of WT1 and ACE mRNAs from blood EVs of DN patients showed upregulated expression of WT1 mRNA and downregulated expression of ACE mRNA in DN patients compared to DM patients and controls. Moreover, WT1 and ACE mRNAs from blood EVs were associated with the severity of albuminuria and showed good diagnostic performance to discriminate DN from DM [41]. This study, in agreement with our study, indicated the important role of mRNA from blood EVs in DN development and also showed that exploring more mRNA profiles of blood EVs in DN will lead to a better understanding of DN pathophysiology and the discovery of alternative biomarkers for DN management.…”

Section: Plos Onesupporting

confidence: 90%

The role of CDH2 and MCP-1 mRNAs of blood extracellular vesicles in predicting early-stage diabetic nephropathy

et al. 2022

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Background Extracellular vesicles (EVs), including exosomes and microvesicles, are involved in intercellular communication by transferring biomolecules such as mRNA, which has been shown to be as essential biomarkers for many physiological and pathological conditions such as diabetic nephropathy (DN). This study aimed to investigate the expression of CDH1, CDH2, MCP-1, and PAI-1 mRNAs in blood EVs of DN patients and to determine their accuracy in predicting early-stage DN. Methods We recruited 196 participants, including 35 overt DN patients, 53 incipient DN patients, 62 diabetic patients (DM), and 46 healthy individuals. Quantification of the mRNA profile of blood EVs was performed using the qRT-PCR method. The diagnostic performance of mRNA was evaluated using receiver operating characteristic analysis. Results The mRNA expression of CDH2 and MCP-1 was downregulated in overt DN group (0.22-fold change and 0.15-fold change, respectively) and incipient DN group (0.60-fold change and 0.43-fold change, respectively) compared to DM group (1.72-fold change and 2.77-fold change, respectively), while PAI-1 mRNA expression decreased in incipient DN group (0.70-fold change) and DM group (0.58-fold change) compared to control. However, the expression level of CDH1 mRNA was not significantly different among the four groups (p = 0.408). Moreover, CDH2 and MCP-1 mRNAs inversely correlated with creatinine (r = -0.370 and r = -0.361, p<0.001) and Alb/Cr ratio (r = -0.355 and r = -0.297, p<0.001). 1/CDH2 mRNA also predicted overt DN with an accuracy of 0.75 (95%CI: 0.65–0.85) and incipient DN with an accuracy of 0.61 (95%CI: 0.50–0.71) while 1/MCP-1 mRNA had an accuracy of 0.66 (95%CI: 0.55–0.77) for overt DN prediction and an accuracy of 0.61 (95%CI: 0.51–0.71) for incipient DN prediction. Conclusion CDH2 and MCP-1 mRNAs expression in blood EVs was decreased with the development of DN, suggesting the renoprotective effect of these mRNAs in diabetic individuals. Moreover, their quantifications could serve as diagnostic biomarkers for early-stage DN.

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Section: Plos Onesupporting

confidence: 90%

The role of CDH2 and MCP-1 mRNAs of blood extracellular vesicles in predicting early-stage diabetic nephropathy

et al. 2022

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“…It is shown that sACE is significantly related to the infection mechanism of novel coronavirus (SARS-CoV-2) and can be used to diagnose patients with such infection [ 23 ]. sACE can also be used as a serum exosomal messenger RNA (mRNA) indicator to diagnose early diabetic nephropathy [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and Staging Value of Serum Angiotensin-Converting Enzyme in Sarcoidosis

Wang

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To investigate the diagnostic and staging value of serum angiotensin-converting enzyme (sACE) in sarcoidosis. Methods. Patients with suspected sarcoidosis treated in the Department of Pulmonary and Critical Care Medicine of the China-Japan Friendship Hospital from 2010 to 2020 were included. The data of sACE, erythrocyte sedimentation rate (ESR), complete blood count (CBC), lung function, bronchoalveolar lavage, and biopsy were collected. The differences between the sarcoidosis group and the nonsarcoidosis group and between different stages of sarcoidosis were compared. The receiver operating characteristic (ROC) curve analysis was used for the diagnostic test of sACE in sarcoidosis. Results. A total of 84 cases with suspected sarcoidosis were included, among which 70 cases were confirmed to be sarcoidosis by biopsy. The mean value of sACE in sarcoidosis patients was 56.61 ± 30.80 U/L, which was significantly higher than that in nonsarcoidosis patients ( 28.07 ± 14.11 U/L, P = 0.001 ). The level of sACE in sarcoidosis patients with peripheral superficial lymph nodes and multiple system involvement was significantly higher than that in intrathoracic sarcoidosis patients ( P = 0.009 ); the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) of sarcoidosis patients was 45.39 ± 22.87 %, which was significantly higher than that of nonsarcoidosis patients ( P < 0.001 ). There was no correlation between sACE and ESR ( correlation coefficient = − 0.167 ). According to ROC curve analysis, when sACE ≥ 44.0 U/L, the sensitivity of sarcoidosis diagnosis was 61.4%, the specificity was 92.9%, and the AUC was 0.819. Conclusion. sACE has a good specificity in the diagnosis of sarcoidosis. sACE values in patients with sarcoidosis with systemic involvement were higher than those with simple intrathoracic sarcoidosis.

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“…Current new biomarkers mainly target diagnoses of inflammation, endothelial damage, fibrosis, endothelial dysfunction, and kidney damage, 141 including TNF-α receptor, 142 intercellular adhesion molecule-1, 143 endostatin, 144 copeptin, 145 kidney injury molecule-1, 146 , 147 monocyte chemoattractant protein-1, 148 and neutrophil gelatinase-associated lipocalins. 149 Extracellular vesicles have recently attracted interest, 150 because they are essentially exosomes and particles 151 that transport miRNA, 152 mRNA, 153 , 154 and proteins, 155 and might serve as early biomarkers of DKD. In addition to individual biomarkers, other approaches such as proteomics, 156 genomics, 157 and metabolomics 158 all play roles in screening, especially in studies of chronic kidney disease (CKD) 159 which can predict the development of proteinuria.…”

Section: Introductionmentioning

confidence: 99%

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Liu

et al. 2023

Sig Transduct Target Ther

115

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Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on a single vascular complication are no longer suitable for the long-term management of patients with diabetes. Diabetic panvascular disease (DPD) is a clinical syndrome in which vessels of various sizes, including macrovessels and microvessels in the cardiac, cerebral, renal, ophthalmic, and peripheral systems of patients with diabetes, develop atherosclerosis as a common pathology. Pathological manifestations of DPDs usually manifest macrovascular atherosclerosis, as well as microvascular endothelial function impairment, basement membrane thickening, and microthrombosis. Cardiac, cerebral, and peripheral microangiopathy coexist with microangiopathy, while renal and retinal are predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, and risk-predictive relationships between diseases. Aggressive glycemic control combined with early comprehensive vascular intervention is the key to prevention and treatment. In addition to the widely recommended metformin, glucagon-like peptide-1 agonist, and sodium-glucose cotransporter-2 inhibitors, for the latest molecular mechanisms, aldose reductase inhibitors, peroxisome proliferator-activated receptor-γ agonizts, glucokinases agonizts, mitochondrial energy modulators, etc. are under active development. DPDs are proposed for patients to obtain more systematic clinical care requires a comprehensive diabetes care center focusing on panvascular diseases. This would leverage the advantages of a cross-disciplinary approach to achieve better integration of the pathogenesis and therapeutic evidence. Such a strategy would confer more clinical benefits to patients and promote the comprehensive development of DPD as a discipline.

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WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy

Cited by 10 publications

References 39 publications

The role of CDH2 and MCP-1 mRNAs of blood extracellular vesicles in predicting early-stage diabetic nephropathy

The role of CDH2 and MCP-1 mRNAs of blood extracellular vesicles in predicting early-stage diabetic nephropathy

Diagnostic and Staging Value of Serum Angiotensin-Converting Enzyme in Sarcoidosis

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

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