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Diabetic nephropathy (DN) is a frequent and severe microvascular complication of diabetes. Glomerular mesangial cell (MC) injury occurs at the initial phase of DN and acts as a critical role in the pathogenesis of DN. Given the importance of long non-coding RNA (lncRNA) in regulating MC hyperplasia and extracellular matrix (ECM) accumulation, it is essential to identify functional lncRNAs during MC injury. Here a novel lncRNA, C920021L13Rik (L13Rik for short), was identified to up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic rats was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik on regulating HG-induced MC injury was assessed using cell counting kit-8 (CCK-8) and western blot assay to analyze MC viability and ECM accumulation. We found that L13Rik level was significantly increased while miR-2861 level was significantly decreased in peripheral blood of DN patients, renal tissues of diabetic rats, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced MC survival, ECM accumulation, and cell hypertrophy. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of its target cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to accelerate MC injury. Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN, and may be a hopeful therapeutic target for DN.

Glomerular mesangial cell hypertrophy is one of the earliest pathological abnormalities of diabetic nephropathy (DN). A growing literature suggests that lncRNA is involved in the development of DN. However, the function of lncRNA in mesangial cell hypertrophy is still unclear. In the current study, we identified that lncRNA L13Rik was upregulated in DN patients, diabetic rat model and high glucose (HG)-induced mesangial cell. CCK8, Tunel, and western-blot assay were performed to verify the function of silenced L13Rik on the cell growth, apoptosis, and cell hypertrophy in HG-induced mesangial cells. L13Rik knockdown inhibited HG-induced cell proliferation and hypertrophy, while accelerating HG-induced cell apoptosis. Mechanismly, L13Rik regulated mesangial cell hypertrophy by sponging miR-2861. The effect of L13Rik on mesangial hypertrophy was blocked by miR-2861. In addition, L13Rik/miR-2861 promoted mesangial cell hypertrophy by regulating Cyclin-dependent kinase inhibitor 1B (CDKN1B) expression. Taken together, our data showed that L13Rik,as a sponge for miR-2861,regulated protein translation of CDKN1B and led to the hypertrophy of mesangial cell.

Objective: To develop and internally validate a multivariable prediction model based on simple clinical record data and laboratory tests and to estimate the probability of left-ventricular diastolic dysfunction (LVDD) in stable maintenance hemodialysis (MHD) patients without clinical heart failure. Design: Cross-sectional study. Setting and Participants: In all, 181 patients on MHD without clinical heart failure were eligible from the dialysis center of Tongren Hospital, Shanghai Jiao Tong University School of Medicine between October 2017 and September 2018. Outcomes: LVDD detected by echocardiography. Measurements: We performed multivariable logistic regression using demographic, clinical, and laboratory data to identify predictors of LVDD with internal validation by using 200 bootstrap replications. Results: Overall, 78 out of 181 (43.1%) patients were affected by LVDD. Predictors included in the LVDD Model were high-sensitive cardiac troponin T (OR 5.91 per 1-ln unit; 95% CI 2.17–16.13), B-type natriuretic peptide (OR 2.35 per 1-ln unit; 95% CI 1.14–4.86), and dialysis vintage (OR 1.04 per 1-month; 95% CI 1.01–1.07). The area (AUC) under the receiver operating characteristic curve of the Model was 0.871 (95% CI 0.811–0.932, p < 0.001). The calibration plot showed good agreement between predicted and observed probabilities with a calibration slope of 1.023 and intercept of –0.010. After internal validation, the Model maintained excellent discrimination (AUC 0.858, 95% CI 0.798–0.919) and good calibration (slope of 1.079, 95% CI 1.058–1.097 and intercept of –0.120, 95% CI –0.142 to –0.093). LVDD Model Limitation: External validation of the Model will be required. Conclusions: A model using routinely available simple clinical record data and laboratory tests can accurately predict the risk of LVDD in stable MHD patients. The Model and its cutoff values may be useful for early diagnosis and intervention of LVDD.

To identify the relationship between serum high-sensitive cardiac troponin T (hs-cTnT) and left ventricular diastolic dysfunction (LVDD) among maintenance hemodialysis patients and to further explore the value of hs-cTnT in evaluating and predicting LVDD in this special group of patients.In a cross-sectional study, 152 dialysis patients with end-stage renal disease (ESRD) underwent Hs-cTnT measurement using the high sensitivity assay. Echocardiography measurements were carried out according to the American Society of Echocardiography recommendations and E/E' 15 or E' 7 cm/s was defined as diastolic dysfunction. Demographic, biochemical, and echocardiographic values of left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), left atrial diameter, early/late peak velocities ratio (E/A), early peak diastolic annular velocity (E') and E/E' were compared across quartiles of hs-cTnT. The association of plasma hs-cTnT concentrations with echocardiographic parameters was analyzed by Spearman's correlation. The relationship between serum hs-cTnT and LVDD parameters of E/E' and E' was analyzed using multivariate regression analysis, and the value of hs-cTnT on assessing LVDD was evaluated by receiver-operating characteristic (ROC) curves.The median value of hs-cTnT was 45 pg/ml (range 28-73). All patients had detectable hs-cTnT, while 88% had greater hs-cTnT than the 99th percentile of the general population (14 pg/ml). Serum hs-cTnT values showed a significantly positive correlation with E/E' (r = 0.739, p 0.001) and LVMI (r = 0.608, p 0.001), but showed a negative correlation with E' (r = - 0.554, p 0.001). Serum hs-cTnT was not associated with LV systolic dysfunction. The associations of hs-cTnT with E/E' and E' persisted after multivariate adjustment for LVMI and comorbidities. In logistic multiple regression analysis, compared with the lowest quartile of hs-cTnT, the highest two quartiles were approximately 5 and 11 times more likely to have E/E' 15 and 7 and 17 times more likely to have E' 7 cm/s. The area under the ROC curve for hs-cTnT evaluating E/E' 15 was 0.847 and evaluating E' 7 cm/s was 0.799, which denoted a moderate accuracy.Our studies suggest that serum hs-cTnT may serve as a biomarker of LVDD in hemodialysis patients.

This study aimed to investigate the molecular mechanisms of diabetic kidney disease (DKD) and to explore new potential therapeutic strategies and biomarkers for DKD. First we analyzed the differentially expressed changes between patients with DKD and the control group using the chip data in Gene Expression Omnibus (GEO) database. Then the gene chip was subjected to be annotated again, so as to screen long noncoding RNAs (lncRNAs) and study expression differences of these lncRNAs in DKD and controlled samples. At last, the function of the differential lncRNAs was analyzed. A total of 252 lncRNAs were identified, and 14 were differentially expressed. In addition, there were 1,629 differentially expressed messenger RNAs (mRNAs) genes, and proliferation and apoptosis adapter protein 15 (PEA15), MIR22, and long intergenic nonprotein coding RNA 472 ( LINC00472) were significantly differentially expressed in DKD samples. Through functional analysis of the encoding genes coexpressed by the three lncRNAs, we found these genes were mainly enriched in type 1 diabetes and autoimmune thyroid disease pathways, whereas in Gene Ontology (GO) function classification, they were also mainly enriched in the immune response, type I interferon signaling pathways, interferon-γ mediated signaling pathways, and so forth. To summary, we identified EA15, MIR22, and LINC00472 may serve as the potential diagnostic markers of DKD.

Diabetic nephropathy (DN) is one of the most common and serious complication in diabetes patients. However, the evidences of gene regulation mechanism and epigenetic modification with DN remain unclear. Therefore, it is necessary to search regulating genes for early diagnosis on DN. We identified tissue specific genes through mining the gene expression omnibus (GEO) public database, enriched function by gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) analysis, and further compared tissue-specific network. Meanwhile, combining with differentially methylated sites, we explored the association epigenetic modification with the pathogenesis of DN. Glomeruli (Glom) may be the main tissue of signal recognition and tubulointerstitium (Tub) is mainly associated with energy metabolism in the occurrence of DN. By comparing tissue-specific networks between Glom and Tub, we screened 319 genes, which played an important role in multiple tissue on kidney. Among them, ANXA2, UBE2L6, MME, IQGAP, SLC7A7, and PLG played a key role in regulating the incidence of DN. Besides, we also identified 1 up-regulated gene (PIK3C2B) and 39 down-regulated genes (POLR2G, DDB1, and ZNF230, etc.) in the methylated data of Glom specific genes. In the Tub specific expressed genes, we identified two hypo-methylated genes (PPARA and GLS). Tub mainly caused abnormal energy metabolism, and Glom caused the changes in cell connections and histone modification. By analyzing differentially methylated sites and tissue-specific expressed genes, we found the change of methylated status about the core regulating genes may be a potential factor in the pathogenesis of DN.