Upregulation of MiR-126 Delays the Senescence of Human Glomerular Mesangial Cells Induced by High Glucose via Telomere-p53-p21-Rb Signaling Pathway

Diabetic kidney disease (DKD)is a microvascular complication of type 2 diabetes.The study of DKD mechanisms is the most important target for the prevention of DKD.Renal senescence is one of the important pathogeneses for DKD,but the mechanism of renal and cellular senescence is unclear.Decreased expression of circulating miR-126 is associated with the development of DKD and may be a promising blood-based biomarker for DKD.This study is to probe the effect and mechanism of miR-126 on the aging of human glomerular mesangial cells (HGMCs)induced by high glucose.HGMCs were cultured with Roswell Park Memorial Institute (RPMI-1640)in vitro.The effect of high glucose on morphology of HGMCs was observed 72h after intervention.The cell cycle was examined by flow cytometry.The telomere length was measured by Southern blotting.The expression levels of p53,p21 and Rb proteins in p53-p21-Rb signaling pathway and p-statl,p-stat3 in JAK/STAT signaling pathway were detected by Western blotting respectively.The expression of miR-126 was examined by qRT-PCR.MiR-126 mimics was transfected into HGMCs.The effects of miR-126 mimics transfection on cell morphology,cell cycle,telomere length,p53,p21,Rb,p-stat1 and p-stat3 were observed. The results showed that high glucose not only arrested the cell cycle in G1phase but also shortened the telomere length.High glucose led to high expression of p53,p21,Rb,p-statl and p-stat3 and premature senescence of HGMCs by activating the telomere-p53-p21-Rb and JAK/STAT signaling pathways.Moreover,the miR-126 was decreased in HGMCs induced by high glucose.It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs.The results may serve as a new strategy for the treatment of DKD.

Relationship between pulmonary hypertension and cardiovascular events, all-cause death in maintenance hemodialysis patients

Objective: To determine the impact of pulmonary hypertension (PH) on maintenance hemodialysis (MHD) patients' cardiovascular events and all-cause mortality. Methods: We included 90 MHD patients, divided into group with PH and group without PH. All patients had been followed up for 4 years, and the primary endpoints were all cause mortality and cardiovascular events. We compared the clinical data and the endpoint events between the two groups. Results: We found PH in 37 patients (41.11%). The incidence of previous cardiovascular disease in group with PH was significantly higher than that in group without PH (χ2=2.034, P < 0.05). The left atrial diameter in group with PH was significantly higher than that in group without PH (t = 7.265, P < 0.01). Logistic regression analysis revealed that previous cardiovascular disease and left atrial diameter were the independent determinants of PH. The rate of new cardiovascular events in group with PH(59.5%) was significantly higher than that in group without PH(34%) (χ2=9.203, P < 0.05). The associated variables of cardiovascular events were:systolic pulmonary arterial pressure, age, history cardiovascular disease, hs-CRP, ejection fraction, left ventricular diastolic dysfunction. In a multivariate model, the PH maintained its independent association. The mortality rate in group with PH (48.6%) was significantly higher than that in group without PH (26.4%) (χ2=5.049, P <0.05). In the Cox survival analysis, we found an association between mortality and systolic pulmonary arterial pressure, age, previous cardiovascular disease, Alb, ejection fraction. In a multivariate model the PH remains as independent predictor of mortality. Conclusion:Pulmonary hypertension is common in HD patients and a valuable predictor of mortality and cardiovascular events.