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Diabetes nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide, and podocyte injury is the central contributor to the progression of DN. Despite the emerging evidence that has established the importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of DN, abnormal protein O-GlcNAcylation is also augmented. Currently, the mechanism associating these two hyperglycemia-induced disorders remains poorly understood. This study intended to elucidate whether ER stress drives hyper-protein O-GlcNAcylation to cause podocyte injury in DN. We used both type 1 and type 2 DN models to confirm the occurrence of ER stress and excessive protein O-GlcNAcylation, and then podocyte purification was also conducted for further investigation. Nephroseq V5 data were mined and in vitro studies were applied to reveal the involvement of ER stress and hyper-O-GlcNAcylation in podocyte injury. Our results indicated that ER stress was induced in both type 1 and type 2 DN, and the human RNA-seq data from Nephroseq V5 showed that O-GlcNAcylation-related genes were significantly upregulated in the DN patients. We further demonstrated that ER stress occurred prior to hyper-O-GlcNAc modification and that pharmacologically inhibited protein O-GlcNAcylation can help decrease the podocyte apoptosis induced by hyperglycemia. Together, these discoveries will aid in uncovering the activation of the ER stress–O-GlcNAcylation axis in podocyte injury under DN, which will help open up new therapeutic approaches for preventing DN progression. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) and primary glomerular disease (PGD) are the main causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). This study was conducted to compare the characteristics of ambulatory blood-pressure monitoring (ABPM) and its relationship with target-organ damage (TOD) in patients with DKD and PGD matched by propensity score. The assessment of TOD included macroalbuminuria, left ventricular hypertrophy (LVH) and macrovascular disease. Propensity-score weighting (PSW) was used in stratified analysis. Results: Patients with DKD had a higher prevalence of abnormal blood-pressure patterns such as reversed dipper pattern, nocturnal hypertension, and sustained hypertension and had a higher prevalence of TOD than did patients with PGD. Logistic regression indicated that patients with DKD were more related to TOD than to PGD. The stratified analysis indicated that DKD patients with white-coat hypertension, masked hypertension and sustained hypertension had closer relationships with TOD compared with PGD patients. Conclusion: Patients with type 2 diabetic kidney disease had more abnormal blood-pressure patterns and were more closely related to target organ damage than were patients with primary glomerular disease. [ABSTRACT FROM AUTHOR]

17β-estradiol (17β-E2) has been implicated in inhibiting the senescence of vascular endothelial cells (VEC) and slowing down the process of atherosclerosis. However, the underlying molecular mechanisms are still unknown. In this study, we examined the roles of SIRT3 in 17β-E2-induced autophagy and 17β-E2-mediated inhibition of hydrogen peroxide (H2O2)-induced senescence in Human umbilical vein endothelial cells (HUVEC). Cellular senescence was measured by immunoblot analysis with antibodies against phosphorylated Rb and senescence-associated β-galactosidase staining. Immunoblot analysis with antibodies against LC3 and p62 was performed to determine autophagy flux. Our findings show that 17β-E2 activates SIRT3 promoter and upregulates SIRT3 gene expression in HUVEC cells. siRNA-mediated silencing of SIRT3 gene expression inhibits 17β-E2-induced processing of LC3-I to LC3-II and degradation of p62, two widely-used makers of autophagy. SIRT3 knockdown also blocks 17β-E2-induced inhibition of cellular senescence triggered by H2O2. Our data further reveal that SIRT3 knockdown impairs 17β-E2-induced co-localization of LC3 and VDAC1, a marker protein on mitochondria, when HUVEC cells were co-treated with H2O2. Together, our findings suggest that 17β-E2 upregulates SIRT3 gene expression by activating SIRT3 promoter and then promotes autophagy, which in turn serves to remove dysfunctional mitochondria caused by H2O2 and consequently inhibit H2O2-induced senescence in HUVEC cells. [ABSTRACT FROM AUTHOR]