Biomarkers of diabetic nephropathy: A 2017 update

Papadopoulou-Marketou, Nektaria; Kanaka‐Gantenbein, Christina; Marketos, Nikolaos; Chrousos, George P.; Papassotiriou, Ioannis

doi:10.1080/10408363.2017.1377682

Cited by 103 publications

(76 citation statements)

References 159 publications

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“…The chronic kidney disease mortality rate was reported to have increased by 26.8% primarily because of DN (69.1%) (1). The pathogenesis of DN is closely related to a variety of factors, including the presence of glomerular mesangial lesions, the proliferation of mesangial cells (MCs), and the accumulation of extracellular matrix (ECM) (2). It has been known that the accumulation of ECM and proliferation of MCs are the major recognized features of glomerulosclerosis in DN (3).…”

mentioning

confidence: 99%

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

et al. 2019

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Evidence has shown that long noncoding RNAs (IncRNAs) in the competing endogenous RNA (ceRNA) network are involved in various diseases. However, there is a lack of studies of the ceRNA network in diabetic nephropathy (DN). In this study, we investigated the effect of IncRNAs on mesangial cell (MC) proliferation in DN‐related ceRNA networks. Differences in IncRNA and mRNA expression between DN and normal mouse kidney tissues were detected with RNA‐seq, and DN‐related IncRNA/mRNA/microRNA (miRNA) ceRNA networks were constructed by R3.4.3. Computational analysis was performed, and expression and interactions between the topological RNAs were detected by bioinformatics methods, real‐time quantitative PCR (qPCR), and luciferase assay. Cell proliferation ability was measured by 5‐ethynyl‐2′‐deoxyuridine (EdU) in MCs cultured under high‐ or low‐glucose conditions. Moreover, the effect of the topological key IncRNA histocompatibility 2 K region locus 2 (H2k2) H2k2 on MC proliferation via the miRNA (miR)‐449a/b/triplet motif 11 (Trim11)/Mek signaling pathway was examined by EdU, flow cytometry analysis, and Western blot. In total, 153 IncRNAs, 428 mRNAs, and 2242 interactions were included in the constructed DN‐related ceRNA network. There were 15 RNAs in the top 5% of degree and betweenness. The expression of IncRNA H2k2 and mRNA Trim11 in MCs was increased in DN, which is consistent with the results of RNA‐seq and real‐time qPCR in vivo and in vitro. miR‐449a and miR‐449b, which were down‐regulated in MCs cultured with high glucose, were selected for further analysis. The results of real‐time qPCR and luciferase assay revealed the IncRNA H2k2‐miR‐449a/b‐Trim11 interaction in MCs. In addition, the data showed that H2k2 regulates MC proliferation via the miR‐449ab/Trim11/Mek signaling pathway. Taken together, these results provide new insight into the association between the topological key IncRNA H2k2 in the DN‐related ceRNA network and the miR‐449a/b/Trim11/Mek signaling pathway during MC proliferation in DN.—Chen, W., Peng, R., Sun, Y., Liu, H., Zhang, L., Peng, H., Zhang, Z. The topological key IncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR‐449a/b/Trim11/Mek signaling pathway. FASEB J. 33, 11492–11506 (2019). http://www.fasebj.org

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confidence: 99%

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

et al. 2019

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“…Ljubic et al, 2015 [25] were attributed the decreases of adiponectin levels in T2DM patients to obesity. Notably, Jung et al, [20] suggested that renal ADPN degradation is already impaired in patients with mild to moderate renal insufficiency. Our results were in disagreement with Galovicova et al, 2012 [26] who reported higher plasma adiponectin levels in those with Macroalbuminuria, compared to those who had normoalbuminuria as well as nicroalbuminuria concluding that diabetic nephropathy potentially plays a very important role in increasing the synthesis and secretion of adiponectin.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin level in diabetic kidney disease the relationship with glycemic control and microvascular complications; a mystery unresolved

Tony¹,

Mostafa²,

Abd-Elaal³

et al. 2018

IJM

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Background:Defining new predictive biomarkers in diabetic kidney disease (DKD) would provide a window of opportunity for preventive and/or therapeutic interventions to prevent or delay the onset of irreversible long-term micro and or macro vascular complications. Adiponectin (ADPN) has been variously associated with diabetic microvascular complications; however, no comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications. Aim of study: we aimed to measure the plasma levels of adiponectin in patients with type 2 diabetes mellitus, to assess whether these levels vary with the different stages of DKD according to their e GFR and to evaluate its relation to their microvascular complications and glycemic control. Methods: This is a prospective observational study including 100 T2DM classified into two groups according to their albuminuria levels and estimated GFR. Participants subjected to thorough history taking and clinical examination. Serum level of ADPN was assessed in all patients. Results: Serum ADPN levels were significantly lower in T2DM patients with nephropathy (P = 0.001), while their levels were nonsignificantly higher in patients with non-proliferative retinopathy or neuropathy. Their levels were lowered with more advanced stages of DKD with nephropathy and the decrement was dependent on their severity (P<0.001). Levels of ADPN with cutoff value of < 22600 (μg/mL) had ability to diagnose microvascular complications in our diabetic patients with sensitivity (81%) and specificity (27%). Multivariate logistic regression analysis showed that the odds ratio for the presence of nephropathy in the lowest tertile of ADPN was 1.09 (95% CI; 11.45-13.08, P= 0.06), therefore, ADPN was not an independent risk factor for diabetic nephropathy. However, its higher level was independently associated with increased odds for the presence of neuropathy in particular. Conclusions: ADPN plays a role in the pathogenesis of microvasculopathy in diabetic patients and help to identify high-risk patients and modulate the therapeutic potential in the prevention of DKD.

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“…These novel biomarkers can be classified as: (a) Glomerular biomarkers: Transferrin, immunoglobulin G, ceruloplasmin, type IV collagen, laminin, glycosaminoglycans(GAGs), lipocalin‐type prostaglandin D synthase (L‐PGDS), fibronectin, podocytes‐podocalyxin, and vascular endothelial growth factor (VEGF); (b) Tubular biomarkers: neutrophil gelatinase‐associated lipocalin (NGAL), α‐1‐microglobulin, kidney injury molecule 1(KIM‐1), N‐acetyl‐β‐D‐glucosaminidase (NAG), cystatin C, and liver‐type fatty acid‐binding protein (L‐FABP); (c) Inflammatory biomarkers: TNF‐α, IL‐1β, IL‐18, interferon gamma induced protein (IP‐10), monocyte chemoattractant protein‐1 (MCP‐1), granulocyte colony‐stimulating factor (G‐CSF), eotaxins, RANTES (regulated on activation, normal T cell expressed and secreted) or CCL‐5; (d) Biomarkers of oxidative: 8‐oxo‐7,8‐dihydro‐2‐deoxyguanosine (8oHdG); (e) Others: podocalyxin, nephrin, AGEs . Although these biomarkers are potentially useful for the evaluation of DKD, none have been validated to improve clinical decision‐making . For example, neutrophil gelatinase‐associated lipocalin (NGAL) is a lipocalin iron‐carrying protein of 25 kDa which belongs to the super family of lipocalins.…”

Section: Quantification Of Urinary Mirnas As Biomarkers For Dkdmentioning

confidence: 99%

“…Hence, although these new biomarkers are promising, further studies are needed before establishing in clinical practice and overcoming the problems of specificity and technical variability . Therefore, it is necessary to explore novel biomarkers to allow accurate identification of kidney injury in DKD and “at risk” individuals.…”

Section: Quantification Of Urinary Mirnas As Biomarkers For Dkdmentioning

confidence: 99%

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MicroRNA as novel biomarkers and therapeutic targets in diabetic kidney disease: An update

et al. 2019

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Diabetic kidney disease (DKD) is a life‐limiting condition characterized by progressive and irreversible loss of renal function. Currently, the estimated glomerular filtration rate (eGFR) and albuminuria are used as key markers to define DKD. However, they may not accurately indicate the degree of renal dysfunction and injury. Current therapeutic approaches for DKD, including attainment of blood pressure goals, optimal control of blood glucose and lipid levels, and the use of agents to block the renin‐angiotensin‐aldosterone system (RAAS) can only slow the progression of DKD. Hence, early diagnosis and innovative strategies are needed to both prevent and treat DKD. In recent years, a novel class of noncoding RNA, microRNAs (miRNAs) are reported to be involved in all biological processes, including cellular proliferation, apoptosis, and differentiation. miRNAs are small noncoding RNAs that regulate gene expression by posttranscriptional and epigenetic mechanisms. They are found to be in virtually all body fluids and used successfully as biomarkers for various diseases. Urinary miRNAs correlate with clinical and histologic parameters in DKD and differential urinary miRNA expression patterns have been reported. Kidney fibrosis is the common end stage of various CKD including DKD. Transforming growth factor‐β(TGF‐β) is regarded as the master regulator of kidney fibrosis, which is likely at least in part through regulating miRNA expression. miRNA are widely involved in the progression of DKD via many molecular mechanisms. In this review, the involvement of miRNA in fibrosis, inflammation, hypertrophy, autophagy, endoplasmic reticulum (ER) stress, oxidative stress, insulin resistance, and podocyte injury will be discussed, as these mechanisms are believed to offer new therapeutic targets that can be exploited to develop important treatments for DKD over the next decade.

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Biomarkers of diabetic nephropathy: A 2017 update

Cited by 103 publications

References 159 publications

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

Adiponectin level in diabetic kidney disease the relationship with glycemic control and microvascular complications; a mystery unresolved

MicroRNA as novel biomarkers and therapeutic targets in diabetic kidney disease: An update

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