Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients

Petrică, Ligia; Hogea, Elena; Gădălean, Florica; Vlad, Adrian; Vlad, Mihaela; Dumitraşcu, Victor; Velciov, Silvia; Gluhovschi, Cristina; Bob, Flaviu; Ursoniu, Sorin; Jianu, Dragoș Cătălin; Matusz, Petru; Pusztai, Agneta-Maria; Motoc, Andrei Gheorghe Marius; Creţu, Octavian; Radu, Dana M.; Milaş, Oana; Golea-Secara, Alina; Simulescu, Anca; Mogos-Stefan, Maria; Patruica, Mihaela; Balint, Lavinia; Ienciu, Silvia; Vlad, Daliborca; Popescu, Roxana

doi:10.7150/ijms.56551

Cited by 15 publications

(20 citation statements)

References 41 publications

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“…Metastasis-associated lung adenocarcinoma transcript 1, also known as Neat2 (Malat1) is one of the most analyzed lncRNAs in DKD samples. The qualitative analysis showed that lncRNAs were expressed in serum, urine, peripheral blood mononuclear cells, and kidney tissue [ 29 , 30 , 36 , 37 , 39 ]. There were increased expressions of lncRNA MALAT1 in DKD, translocation of β -catenin to the nucleus, enhanced expressions of MALAT1 connexin serine/arginine splicing factor 1 (SRSF1), and expressions of p-cadherin and tight junction protein ZO-1.…”

Section: Discussionmentioning

confidence: 99%

The Impact of lncRNA on Diabetic Kidney Disease: Systematic Review and In Silico Analyses

Zhao

Yan

et al. 2022

Computational Intelligence and Neuroscience

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Background. Long noncoding RNA (lncRNA) is involved in the occurrence and development of diabetic kidney disease (DKD). It is necessary to identify the expression of lncRNA from DKD patients through systematic reviews, and then carry out silico analyses to recognize the dysregulated lncRNA and their associated pathways. Methods. The study searched Pubmed, Embase, Cochrane Library, WanFang, VIP, CNKI, and CBM to find lncRNA studies on DKD published before March 1, 2021. Systematic review of the literature on this topic was conducted to determine the expression of lncRNA in DKD and non-DKD controls. For the dysregulated lncRNA in DKD patients, silico analysis was performed, and lncRNA2Target v2.0 and starBase were used to search for potential target genes of lncRNA. The Encyclopedia of Genomics (KEGG) pathway enrichment analysis was performed to better identify dysregulated lncRNAs in DKD and determine the associated signal pathways. Results. According to the inclusion and exclusion criteria, 28 publications meeting the eligibility criteria were included in the systematic evaluation. A total of 3,394 patients were enrolled in this study, including 1,238 patients in DKD group, and 1,223 diabetic patients, and 933 healthy adults in control group. Compared with the control, there were eight lncRNA disorders in DKD patients (MALAT1, GAS5, MIAT, CASC2, NEAT1, NR_033515, ARAP1-AS2, and ARAP1-AS1). In addition, five lncRNAs (MALAT1, GAS5, MIAT, CASC2, and NEAT1) participated in disease-related signal pathways, indicating their role in DKD. Discussion. This study showed that there were eight lncRNAs in DKD that were persistently dysregulated, especially five lncRNAs which were closely related to the disease. Although systematic review included 28 studies that analyzed the expression of lncRNA in DKD-related tissues, the potential of these dysregulated lncRNAs as biomarkers or therapeutic targets for DKD remains to be further explored. Trial registration. PROSPERO (CRD42021248634).

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Section: Discussionmentioning

confidence: 99%

The Impact of lncRNA on Diabetic Kidney Disease: Systematic Review and In Silico Analyses

Zhao

Yan

et al. 2022

Computational Intelligence and Neuroscience

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“…In terms of physiology and pathology, various research groups determined NEAT1 as a prognosis marker for poor survival rates and promoter of tumorigenesis [ 28 , 29 , 30 ]. With regard to DKD, others showed a positive and negative correlation, respectively, between elevated urinary NEAT1 and various podocyte damage markers like synaptopodin and podocalyxin or GFR [ 42 ]. HG-exposed proximal tubular cells (HK-2) or murine MCs (mMCs) exhibited an increase in NEAT1 expression in a dose- or time- dependent manner [ 31 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

The Interplay of NEAT1 and miR-339-5p Influences on Mesangial Gene Expression and Function in Various Diabetic-Associated Injury Models

Reichelt-Wurm

Pregler

Wirtz

et al. 2022

ncRNA

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Mesangial cells (MCs), substantial cells for architecture and function of the glomerular tuft, take a key role in progression of diabetic kidney disease (DKD). Despite long standing researches and the need for novel therapies, the underlying regulatory mechanisms in MCs are elusive. This applies in particular to long non-coding RNAs (lncRNA) but also microRNAs (miRNAs). In this study, we investigated the expression of nuclear paraspeckle assembly transcript 1 (NEAT1), a highly conserved lncRNA, in several diabetes in-vitro models using human MCs. These cells were treated with high glucose, TGFβ, TNAα, thapsigargin, or tunicamycin. We analyzed the implication of NEAT1 silencing on mesangial cell migration, proliferation, and cell size as well as on mRNA and miRNA expression. Here, the miRNA hsa-miR-339-5p was not only identified as a potential interaction partner for NEAT1 but also for several coding genes. Furthermore, overexpression of hsa-miR-339-5p leads to a MC phenotype comparable to a NEAT1 knockdown. In-silico analyses also underline a relevant role of NEAT1 and hsa-miR-339-5p in mesangial physiology, especially in the context of DKD.

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“…On the other hand, recent advances in finding biomarkers of early DKD in diabetic population by omics and molecular-biology also supplied an alternative method. For instance, long noncoding RNAs (lncRNAs) have been suggested to play a role in early development of DKD [ 18 ], and glycated peptides within the urine may predict dysfunction of proximal tubule within the kidney [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Ultrasonography Combined with Blood Biochemistry on the Early Diagnosis of Diabetic Kidney Disease

Lin¹,

Liu²,

Lin³

et al. 2022

Disease Markers

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Objective. Diabetic kidney disease (DKD) has been well recognized as a microvascular complication of diabetes mellitus. Perfusion of intrarenal arteries is closely related with development of DKD. The aim of the present study was to investigate relation of ultrasonography performance of intrarenal arteries and grade of DKD. Methods. From May to December at 2021, a total of 54 DKD patients and 36 non-DKD cases were recruited. Ultrasonography performance of intrarenal and arteries at lower extremity was examined by high-resolution ultrasound diagnostic equipment; maximum (Vsmax) as well as minimum (Vdmin) blood velocity of arteries were recorded, and resistance index (RI) of arteries were calculated. Blood routine and biochemical parameters were determined from clinical laboratory of our hospital. Results. According to eGFR grading, 42.50% of the 54 DKD cases are at Grade 1, and 18.52%, 11.11%, 9.26%, and 18.52% cases were at Grade 2, 3a, 3b, and 4-5, respectively. Blood urea and creatinine were significantly positively related with progress of DKD, while level of Hb was negatively related with DKD. By ultrasonography; we found that Vsmax and Vdmin of main renal artery (MRA), segmental renal artery (SRA), and interlobular renal artery (IRA) were significantly reduced compared with healthy cases; IR of the above arteries was dramatically elevated, and changes of the above data were more obvious than that of lower extremity. Vdmin of MRA, SRA, and IRA was negatively related with grading of DKD, while RI was positively related with the grading. Converging from RI and level of Hb, we found that the level of Hb is positively related with healthy status of the kidney, while RI of the arteries is negatively with that. Conclusions. Resistance index (RI) of intrarenal arteries, obtained from ultrasonography combining with level of hemoglobin (Hb), is the predictor of progress of DKD.

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Long noncoding RNAs may impact podocytes and proximal tubule function through modulating miRNAs expression in Early Diabetic Kidney Disease of Type 2 Diabetes Mellitus patients

Cited by 15 publications

References 41 publications

The Impact of lncRNA on Diabetic Kidney Disease: Systematic Review and In Silico Analyses

The Impact of lncRNA on Diabetic Kidney Disease: Systematic Review and In Silico Analyses

The Interplay of NEAT1 and miR-339-5p Influences on Mesangial Gene Expression and Function in Various Diabetic-Associated Injury Models

Ultrasonography Combined with Blood Biochemistry on the Early Diagnosis of Diabetic Kidney Disease

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