No abstract available.
Diabetes Mellitus, Type 2/*blood ; Diabetic Nephropathies/*blood ; Diabetic Retinopathy/*blood ; Hemoglobins/*metabolism ; Humans ; Male

OBJECTIVETo review the advances of studies on vitamin D receptor and its role in the pathogenesis of diabetic nephropathy.

DATA SOURCESA comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as vitamin D receptor and diabetic nephropathy.

STUDY SELECTIONArticles related to vitamin D receptor and diabetic nephropathy were selected and carefully analyzed.

RESULTSThe ligands as well as construction and tissue distribution of vitamin D receptor were summarized. Pathogenesis of diabetic nephropathy was analyzed. The mechanisms underlying the renoprotective role of vitamin D receptor including inhibition of renin-angiotensin system, anti-inflammation, anti-fibrosis and the reduction of proteinuria were reviewed. Mounting evidences from animal and clinical studies have suggested that vitamin D therapy has beneficial effects on the renal systems and the underlying renoprotective mechanisms of the vitamin D receptor-mediated signaling pathways is a hot research topic.

CONCLUSIONOur study suggests that vitamin D receptor has a great potential for preventing the progression of diabetic nephropathy via multiple mechanisms.

Animals ; Diabetic Nephropathies ; metabolism ; Humans ; Proteinuria ; metabolism ; Receptors, Calcitriol ; metabolism ; Renin-Angiotensin System ; physiology

ObjectiveDiabetic kidney disease (DKD) has become one of the major causes of end-stage renal disease. Urinary extracellular vesicles (uEVs) contain rich biological information which could be the ideal source for noninvasive biomarkers of DKD. This review discussed the potential early diagnostic and therapeutic values of proteins and microRNAs in uEVs in DKD.

Data SourcesThis review was based articles published in PubMed, Embase, Cochrane, and Google Scholar databases up to November 20, 2017, with the following keywords: "Diabetic kidney disease", "Extracellular vesicle", and "Urine".

Study SelectionRelevant articles were carefully reviewed, with no exclusions applied to the study design and publication type.

ResultsThere is no "gold standard" technology to separate and/or purify uEVs. The uEVs contain a variety of proteins and RNAs and participate in the physiological and pathological processes of the kidney. UEVs, especially urinary exosomes, may be useful biomarkers for early diagnosis and treatment to DKD. Furthermore, the uEVs has been used as a therapeutic target for DKD.

ConclusionProteins and nucleic acids in uEVs represent promising biomarker for the diagnosis and treatment of DKD.

Biomarkers ; metabolism ; Databases, Factual ; Diabetic Nephropathies ; diagnosis ; metabolism ; Extracellular Vesicles ; metabolism ; Humans

Animals ; Apoptosis ; Diabetic Nephropathies ; metabolism ; pathology ; Glucose ; metabolism ; Membrane Potential, Mitochondrial ; Mice ; Mice, Transgenic ; Mitochondria ; pathology ; Podocytes ; cytology

OBJECTIVETo explore the podocyte injury in patients with diabetic nephropathy (DN) and analyze its relationship with glucose regulated protein 78 (GRP78) and proteinuria.

METHODSThe clinical data of 48 patients diagnosed as DN by renal biopsy were reviewed. All patients were divided into two groups according to proteinuria (>3.5 g/d, n=31 and 3.5 g/d, n=17). The density of podocytes was illustrated by immunohistochemistry staining of Wilms tumor-1 (WT-1), and the immunofluorescence double-staining results of synaptopodin and GRP78 in podocytes were detected.

RESULTSThe podocyte dentistry of urine protein > 3.5 g/d group was significantly lower than that of urine protein>3.5 g/d group urine protein<3.5 g/d group(P=0.003), and it was negatively correlated with proteinuria (P=0.005). The expressions of synaptopodin and GRP78 in podocytes were also negatively correlated with proteinuria (P=0.004 and P=0.001).

CONCLUSIONThe podocyte injury is aggravated with increased proteinuria in DN patients, along with the decrease of the adaptive ability of endoplasmic reticulum to stress.

Adult ; Diabetic Nephropathies ; complications ; metabolism ; pathology ; Female ; Heat-Shock Proteins ; metabolism ; Humans ; Male ; Middle Aged ; Podocytes ; pathology ; Proteinuria ; etiology

OBJECTIVE: To study the therapeutic mechanism of Longqi Fang (LQF) for diabetic kidney disease (DKD) based on GEO database and network pharmacology. METHODS: LQF and DKD targets were obtained using the databases including GEO, TCMSP, CNKI, ChemDraw, and SwissTarget Prediction, and LQF-DKD intersection targets were obtained with VENNY. String was used for protein-protein interaction (PPI) analysis, and R package for KEGG and GO enrichment analysis. Cytoscape 3.7.2 software Network graphs were constructed. The results of network pharmacology analysis were verified in SD rat models of DKD by daily treatment of the rats with LQF at low (1 g/kg), medium (2 g/kg), and high (2 g/kg) doses, and kidney pathology was observed with HE staining and the changes in renal function were assessed. Western blotting was used to detect the expression levels of NF-κB and p-NF-κB proteins. RESULTS: We identified 760 main targets of LQF, and obtained 1026 differential genes using GEO database and 61 LQF-DKD intersection targets using Venny database. The core targets obtained through PPI network analysis included Myc, EGF, CASP3, VEGFA, CCL2, SPP1, VCAM1 and ICAM1. Go analysis showed that LQF affects mainly nuclear receptor activity and ligand activated transcription factor activity. KEGG analysis showed that LQF affects inflammatory signaling pathways by interfering with NF-κB, TNF, and PI3K-AKT. In rat models of DKD, treatment with LQF resulted in significant improvements of the renal functions (P < 0.05) and glomerular and tubular structure and arrangement in a dose-dependent manner. Western blotting results showed that LQF dose-dependently downregulated NF-κB and p-NF-κB expressions in the rat models. CONCLUSION The therapeutic mechanism of LQF for DKD involves multiple components, targets and signal pathways that mediate an inhibitory effect on NF-κB signaling pathway to protect the renal function.
Animals ; Diabetes Mellitus ; Diabetic Nephropathies/metabolism* ; Network Pharmacology ; Phosphatidylinositol 3-Kinases/metabolism* ; Protein Interaction Maps ; Rats ; Rats, Sprague-Dawley

OBJECTIVES: The thickening of the glomerular basement membrane in rats after Vacor ingestion was examined by electron microscopy. This study was performed to elucidate which biochemical components changed in the glomerular basement membrane after Vacor-induced diabetic glomerulopathy. METHODS: Immunohistochemical analyses of type IV collagen, laminin, fibronectin and chondroitin sulfate proteoglycan were performed. A single dose of Vacor (molecular weight 272), 80 mg/kg, was administered to adult male Wistar rats by orogastric canule, and the animals were sacrificed at 0.5, 1, 3, 7, 14, 28 and 56 days after administration. RESULTS: Mild thickening of the glomerular basement membrane was evident 7 days after Vacor administration, and the width of the glomerular basement membrane was more than twice that of normal controls at 28 and 56 days. Significantly increased expressions of type IV collagen, laminin, fibronectin and neutral polysaccharide in the thickened glomerular basement membrane were noted 14 to 56 days after administration, and a mildly increased expression of chondroitin sulfate proteoglycan appeared between 3 to 7 days. CONCLUSION: These abnormally increased glomerular basement membrane components might be part of what causes diabetic nephropathy after Vacor administration.
Animal ; Basement Membrane/pathology ; Basement Membrane/metabolism ; Basement Membrane/drug effects ; Diabetic Nephropathies/pathology ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/chemically induced* ; Extracellular Matrix Proteins/metabolism ; Kidney Glomerulus/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/drug effects ; Male ; Phenylurea Compounds/toxicity* ; Proteochondroitin Sulfates/metabolism ; Rats ; Rats, Wistar

Shuangdan oral liquid (SDO) containing radix Salviae miltiorrhizae (Chinese name Danshen) and cortex moutan (Chinese name Mudanpi) is a traditional Chinese medicine using for treating vascular diseases. Danshensu (DSS) is a main effective monomer composition derived from radix Salviae miltiorrhizae and paeonol (Pae) from cortex moutan. Although the two herbs are widely used in traditional Chinese medicine, the pharmacological functions of their active compositions were not reported. Therefore, the research of DSS and Pae in mechanisms and pharmacodynamics interaction can provide scientific evidence to support clinical application. The diabetic nephropathy (DN) rats which were induced by streptozotocin (STZ) were treated with SDO, DSS, Pae, and DSS+Pae for eight weeks. The positive effects on DN animal models were investigated by detection of physiological and biochemical indexes and oxidative stress markers, within five treatments: SDO, DSS, Pae, DSS+Pae and insulin group. Compared with the model group, the DSS+Pae group improved the renal function, blood lipid metabolism and blood viscosity, increased the vitality of T-SOD or T-AOC and decreased the level of MDA or NO after the treatment. The study was successfully showed that the DSS+Pae group could delay the process of DN, especially in the renal injury part of histopathology changes. Our results suggest that the co-administration of DSS and Pae significantly may play a protective role in DN rats through decreasing the oxidative stress and improving the blood lipid metabolism mechanisms.
Animals ; Blood Viscosity ; Diabetic Nephropathies* ; Insulin ; Lipid Metabolism ; Medicine, Chinese Traditional ; Models, Animal ; Oxidative Stress ; Rats* ; Salvia ; Streptozocin ; Vascular Diseases

OBJECTIVEIn order to explore the therapeutic effect of tongxinluo capsule (TXLC) on diabetic nephropathy, the influence on plasma endothelin (ET-1) level of the drug was observed.

METHODSAll the 63 patients enrolled were randomly divided into the treatment group and control group. They were all treated with low protein diabetic diet, oral administration of hypoglycemic or injection of insulin, calcium antagonist according to level of blood pressure and supportive symptomatic treatment. To the treated group, 2 capsules of TXLC were given additionally three times a day. The efficacy was evaluated after 8 weeks' treatment. The chief indices observed before and after treatment were endogenous creatinine clearance rate (CCr), urinary albumin excretion rate (UAER), urinary beta2-microglobulin (beta2-MG), fasting blood-glucose (FBG) and ET-1.

RESULTSBefore treatment, no significant difference was shown in all the tested indices between the treated group and the control group. After treatment, levels of CCr, UAER, beta2-MG, ET-1 and FBG significantly changed in the treated group, showing significant difference as compared with those before treatment (P < 0.05). Moreover, comparison of these indices in the two groups after treatment, excepting FBG, also showed statistical significance (P < 0.01).

CONCLUSIONTXLC shows obvious effect in reducing plasma ET-1 and UAER, it is definitely effective in repairing the renal tubular interstitial damage, and effectively delay the progress of diabetic nephropathy, improve the renal function, and is favorable to ameliorate hyperglycemia auxiliarily.

Albuminuria ; urine ; Capsules ; Diabetic Nephropathies ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Endothelin-1 ; blood ; Female ; Humans ; Male ; Phytotherapy

To investigate the correlation of serum long noncoding RNA-metastasis associated lung adenocarcinoma transcript 1(LncRNA MALAT1) and serum amyloid A(SAA) with diabetic kidney disease. Retrospective research was used, and 40 patients with type 2 diabetes and 80 patients with type 2 diabetic kidney disease patients who were treated in Tianjin Medical University Chu Hsien-I Memorial Hospital from August 2021 to February 2022 were selected, and 40 healthy subjects were selected during the same period. Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect serum LncRNA MALAT1. SAA were detected with enzyme linked immunosorbent assay (ELISA). Automatic biochemistry analyzer was used to detect serum creatinine (CREA) and low-density lipoprotein cholesterol(LDL-C),automatic blood glucose analyzer to detect serum fasting plasma glucose (FPG), automatic glycated hemoglobin analyzer to detect hemoglobin A1C (HbA1c), and automatic immunoassay analyzer to detect urinary albumin to creatinine ratio(UACR). Differences between groups were compared by t test and analysis of variance. Pearson analysis was used to analyze the correlation between MALAT1, SAA and other indicators. Receiver operating characteristic curve(ROC) was used to evaluate the auxiliary diagnostic value of MALAT1 and SAA for diabetic kidney disease. The results showed that MALAT1 and SAA in the diabetic kidney disease with mass albuminuria group were higher than those in the type 2 diabetes mellitus group (q=8.57, P<0.01; q=11.09, P<0.01) and the diabetic kidney disease with microalbuminuria group (q=3.96, P<0.05; q=7.85, P<0.01). MALAT1 had a high correlation with UACR, CREA, SAA, HbA1c and FPG (r value was 0.706, 0.643, 0.578, 0.553, and 0.524, all P<0.01), and SAA had a high correlation with UACR, HbA1c and FPG (r value was 0.664, 0.617, and 0.595, all P<0.01). ROC curve analysis of the diagnostic value of LncRNA MALAT1 and protein SAA for diabetic kidney disease showed that the areas under curve (AUC) were 0.741 and 0.744, respectively. The combined diagnostic value of the two was the greatest (AUC=0.801). In summary, MALAT1 and SAA were elevated in the serum of patients with type 2 diabetes. Their concentrations in the serum of group with diabetic kidney disease were higher than that in the type 2 diabetes group, and the serum concentrations of MALAT1 and SAA in group with mass albuminuria are higher than the group with microalbuminuria. MALAT1 and SAA were both closely related to UACR and HbA1c, and there is a correlation between them. Both of them may have ancillary diagnostic value for diabetic kidney disease.
Humans ; RNA, Long Noncoding/metabolism* ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies/urine* ; Retrospective Studies ; Glycated Hemoglobin ; Serum Amyloid A Protein ; Albuminuria