Multi-omics analysis reveals the potential pathogenesis and therapeutic targets of diabetic kidney disease.

Clinicians have long been interested in understanding the molecular basis of diabetic kidney disease (DKD)and its potential treatment targets. Its pathophysiology involves protein phosphorylation, one of the most recognizable post-transcriptional modifications, that can take part in many cellular functions and control different metabolic processes. In order to recognize the molecular and protein changes of DKD kidney, this study applied Tandem liquid chromatography-mass spectrometry (LC-MS/MS) and Next-Generation Sequencing, along with Tandem Mass Tags (TMT) labeling techniques to evaluate the mRNA, protein and modified phosphorylation sites between DKD mice and model ones. Based on Gene Ontology (GO) and KEGG pathway analyses of transcriptome and proteome, The molecular changes of DKD include accumulation of extracellular matrix, abnormally activated inflammatory microenvironment, oxidative stress and lipid metabolism disorders, leading to glomerulosclerosis and tubulointerstitial fibrosis. Oxidative stress has been emphasized as an important factor in DKD and progression to ESKD, which is directly related to podocyte injury, albuminuria and renal tubulointerstitial fibrosis. A histological study of phosphorylation further revealed that kinases were crucial. Three groups of studies have found that RAS signaling pathway, RAP1 signaling pathway, AMPK signaling pathway, PPAR signaling pathway and HIF-1 signaling pathway were crucial for the pathogenesis of DKD. Through this approach, it was discovered that targeting specific molecules, proteins, kinases and critical pathways could be a promising approach for treating DKD.

Quality of life in peritoneal and hemodialysis patients in China.

BACKGROUND: Much attention has been paid to the quality of life (QOL) in dialysis patients worldwide. However, differences in QOL between peritoneal dialysis (PD) and hemodialysis (HD) patients have not been clearly identified. The objectives of this study were to compare the differences of QOL between PD and HD patients, and to investigate factors contributing to QOL in the Chinese population. METHODS: All patients who received PD or HD more than 3 months were enrolled in the study. The demographic and clinical data were also obtained. SF-36 was used to assess QOL. RESULTS: A total of 190 (91.8%) of 207 dialysis patients were enrolled in the study. PD patients had markedly lower scores on role-physical (RP) and bodily pain (BP) domains than HD patients, but had remarkably higher scores on role-emotional (RE) domain (p < 0.05). While the scores of physical component summary (PCS) and mental component summary (MCS) showed no differences between the two groups (p > 0.05). The results of the multiple linear regression analysis indicated that age and cerebrovascular disease had negative correlations with PCS (p < 0.01), whereas the serum prealbumin level had positive correlation with PCS (p < 0.05). The married status was negatively associated with MCS (p < 0.01). But the higher education level was positively associated with MCS (p < 0.01). CONCLUSIONS: There were no significant differences on QOL between the two dialysis modalities. The possible factors related to QOL were age, cerebrovascular disease, marital status, education, and serum prealbumin levels.

Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications.

Diabetic angiopathy, which includes diabetic kidney disease (DKD), cardio-cerebrovascular disease, and diabetic retinopathy (DR) among other diseases, is one of the most common complications affecting diabetic patients. Among these, DKD, which is a major cause of morbidity and mortality, affects about 40% of diabetic patients. Similarly, DR involves retinal neovascularization and neurodegeneration as a result of chronic hyperglycemia and is the main cause of visual impairment and blindness. In addition, inflammation also promotes atherosclerosis and diabetes, with atherosclerosis-related cardiovascular diseases being often a main cause of disability or death in diabetic patients. Given that vascular diseases caused by diabetes negatively impact human health, it is therefore important to identify appropriate treatments. In this context, some studies have found that the Hippo/Yes-associated protein (YAP) pathway is a highly evolutionarily conserved protein kinase signal pathway that regulates organ growth and size through its effector signaling pathway Transcriptional co-Activator with PDZ-binding motif (TAZ) and its YAP. YAP is a key factor in the Hippo pathway. The activation of YAP regulates gluconeogenesis, thereby regulating glucose tolerance levels; silencing the YAP gene thereby prevents the formation of glomerular fibrosis. YAP can combine with TEA domain family members to regulate the proliferation and migration of retinal vascular endothelial cells (ECs), so YAP plays a prominent role in the formation and pathology of retinal vessels. In addition, YAP/TAZ activation and translocation to the nucleus promote endothelial inflammation and monocyte-EC attachment, which can increase diabetes-induced cardiovascular atherosclerosis. Hippo/YAP signaling pathway provides a potential therapeutic target for diabetic angiopathy, which can prevent the progression of diabetes to DR and improve renal fibrosis and cardio-vascular atherosclerosis.

Antiangiogenic therapy in diabetic nephropathy: A double­edged sword (Review).

Diabetes and the associated complications are becoming a serious global threat and an increasing burden to human health and the healthcare systems. Diabetic nephropathy (DN) is the primary cause of end­stage kidney disease. Abnormal angiogenesis is well established to be implicated in the morphology and pathophysiology of DN. Factors that promote or inhibit angiogenesis serve an important role in DN. In the present review, the current issues associated with the vascular disease in DN are highlighted, and the challenges in the development of treatments are discussed.