Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy

Background: LncRNA AK044604(regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3β play important roles in diabetic nephropathy(DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.Methods: Diabetic db/db mice received Risa-inhibition adeno-associated virus(AAV) via tail vein injection, and intraperitoneal injection of lithium chloride(LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells(MPCs) were cultured and treated with Risa-inhibition lentivirus(LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy,Periodic Acid-Schiff staining, and immunofluorescence staining.Results: Risa and activated GSK3β were overexpressed, but Sirt1 was downregulated in DN mice and high glucosetreated MPCs(P<0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1(P<0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527(P<0.001, db/db+Risa-AAV vs. db/db, HG+Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3β-mediated autophagy of podocytes(P<0.001, db/db+LiCl vs. db/db, HG+LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy.Conclusions: Risa could inhibit autophagy by regulating the Sirt1/GSK3β axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.

Helicobacter pylori Infection is Associated with Occurrence of Proteinuria in Type 2 Diabetes Patients:A Systemic Review and Meta-Analysis

Background:Type 2diabetes (T2DM)patients are susceptible to Helicobacterpylori (HP),and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients;however,this view remains controversial.This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients.In addition,we hope to provide some recommendations to readers in clinical or related fields. Methods:Our meta-analysis was conducted with the methodology of the Cochrane Collaboration.Search strategies were formulated by relevant professionals.Case-control studies that compared the occurrence ofproteinuria in T2DM patients with and without HP infection were involved in our meta-analysis.Relevant English or Chinese studies were searched on online databases before 2018,including PubMed,the Cochrane library,Medline,Google Scholar,the China National Infrastructure,and Wanfang database.The search strategies were "diabetic proteinuria,diabetic microalbuminuria,diabetic albumainuria,diabetic kidney disease,diabetic renal dysfunction,diabetic renal disease,diabetic nephropathy,diabetic complications,and diabetic mellitus,combined with HP."The quality of these involved articles was separately assessed by two investigators using the Newcastle-Ottawa Scale (NOS).Odds ratios (ORs)and associated 95% confidence intervals (CIs)were extracted and pooled using fixed-effects models. Results:Seven studies involving 1029participants were included.The quality of these seven articles was all above five stars as assessed by NOS,and there was no significant publication bias in our meta-analysis.We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection (OR:2.00,95%CI:1.48-2.69). Conclusions:Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients.HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM.