circKMT2E Protect Retina from Early Diabetic Retinopathy through SIRT1 Signaling Pathway via Sponging miR-204-5p.

Objective: To explore the changes of circRNAs in the retina of diabetic patients without diabetic retinopathy (DR) to screen latent protective factor. Methods: The sequencing data of the retina from three diabetic donors that possess no noticeable pathological feature of the retina at ultimate eye inspection and three healthy donative samples were involved in this study. Herein, we carried out bioinformatics analysis to disclose the expression pattern and characteristics of circRNAs on the basis of Gene Ontology as well as KEGG pathway analyses. Then, sequencing data were applied to infer the interaction between selected circRNAs and miR-204-5p. The potential miRNA response elements for the annotated circRNAs and their target gene were speculated using TargetScan as well as miRanda. Results: RNA sequencing detected 28,978 alternative circRNAs. Thereinto, 1063 were expressed with significant difference. circKMT2E was upregulated more than two folds in alloxan-induced diabetic retinal tissues compared with normal retinal tissues, exhibiting an expression trend opposite to miR-204-5p. Bioinformatics analysis showed that circKMT2E have four seed sequences on hsa-miR-204-5p. Thus, circKMT2E was speculated to have function on the basis of sponging miR-204-5p in order to participate in the pathogenetic process of DR. Besides, miR-204-5p was speculated to be able to bind SIRT1, which can interact with its target proteins, and adjusts various cell functions including cellular inflammatory responses, proliferation, as well as apoptosis. Conclusion: The upregulation of circKMT2E in the early stage of DR may be involved in its pathogenesis and may activate the SIRT1 signaling pathway to protect the retina by the sponge function to miR-204-5p.

Serum Adiponectin Level in Different Stages of Type 2 Diabetic Kidney Disease: A Meta-Analysis.

Background: Biomarkers in predicting the stages of nephropathy associated with type 2 diabetes mellitus are urgent, and adiponectin may be a promising biomarker. This meta-analysis examined the association of serum adiponectin level with the stages of type 2 diabetic nephropathy. Methods: Databases including PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), and Wan Fang were searched for published studies on adiponectin and type 2 diabetic kidney disease. The Newcastle-Ottawa scale was used to assess the quality of the literature. STATA 14.0 was used to conduct the statistical analysis. Results: Thirty-four studies with 5254 patients were included in this meta-analysis. The results of this study show that there was no significant difference in serum adiponectin level between normoalbuminuria and the control group (mean difference = -0.42, 95% CI [-1.23, 0.40]), while serum adiponectin level was positively correlated with the severity of type 2 diabetic kidney disease. The serum adiponectin level in type 2 diabetic kidney disease patients ranks as macroalbuminuria > microalbuminuria > normoalbuminuria. Conclusions: Serum adiponectin level might be an important marker to predict the progression of type 2 diabetic kidney disease.