scholarly journals The Interaction of miR-378i-Skp2 Regulates Cell Senescence in Diabetic Nephropathy

2018 ◽  
Vol 7 (12) ◽  
pp. 468 ◽  
Author(s):  
Yi-Chun Tsai ◽  
Po-Lin Kuo ◽  
Mei-Chuan Kuo ◽  
Wei-Wen Hung ◽  
Ling-Yu Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Human Study ◽  
Cell Senescence ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Bioinformatics Analyses ◽  
Type 2 Diabetic

Diabetic nephropathy (DN) is the major cause of end stage renal disease. Proximal tubular epithelial cell (PTEC) injury occurs early in diabetic kidney, and it is correlated with consequent renal failure. Cellular senescence participates in the pathophysiology of DN, but its role remains unclear. We conducted a cross-disciplinary study, including human, in vivo, and in vitro studies, to explore the novel molecular mechanisms of PTEC senescence in DN. We found that HG induced cell senescence in PTECs, supported by enhanced β-galactosidase staining, p53 and p27 expression, and reduced cyclin E levels. Transcriptome analysis of PTECs from a type 2 diabetic patient and a normal individual using next generation sequencing (NGS) and systematic bioinformatics analyses indicated that miR-378i and its downstream target S-phase kinase protein 2 (Skp2) contribute to HG-induced senescence in PTECs. High glucose (HG) elevated miR-378i expression in PTECs, and miR-378i transfection reduced Skp2 expression. Urinary miR-378i levels were elevated in both db/db mice and type 2 diabetic patients, whereas decreased Skp2 levels were shown in proximal tubule of db/db mice and human DN. Moreover, urinary miR-378i levels were positively correlated with urinary senescence-associated secretory phenotype cytokines and renal function in in vivo and human study. This study demonstrates that the interaction between miR-378i and Skp2 regulates PTEC senescence of DN. miR-378i has the potential to predict renal injury in DN. These findings suggest future applications in both therapy and in predicting renal dysfunction of DN.

scholarly journals Autocrine Exosomal Fibulin-1 as a Target of MiR-1269b Induces Epithelial–Mesenchymal Transition in Proximal Tubule in Diabetic Nephropathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yi-Chun Tsai ◽  
Wei-Wen Hung ◽  
Wei-An Chang ◽  
Ping-Hsun Wu ◽  
Ling-Yu Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Mesenchymal Transition ◽  
Cell Communication ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Mesenchymal Transition ◽  
Type 2 Diabetic

Background: Diabetic nephropathy (DN) is an increasing threat to human health and is regarded to be the leading cause of end-stage renal disease worldwide. Exosomes deliver biomolecule massages and may play a key role in cell communication and the progression of DN.Methods: A cross-disciplinary study, including in vivo, in vitro, and human studies, was conducted to explore the cross-talk within proximal tubular epithelial cells (PTECs) in DN. Exosomal protein from PTECs treated with high glucose (HG) was purified and examined using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Next-generation sequencing (NGS) was utilized to analyze RNAs extracted from PTECs from a type 2 diabetic patient and a normal individual. HK-2 cells were used to assess exosomal protein and its modulation and biofunction in DN. Normal individuals and type 2 diabetic patients were enrolled, and nondiabetic db/m mice and diabetic db/db mice were used to validate the molecular mechanism of exosomes in DN.Results: HG stimulated PTECs to increase Fibulin-1 (FBLN1) expression, and PTECs secreted FBLN1 through exosome delivery, thereby inducing epithelial–mesenchymal transition (EMT) in PTECs. Transcriptome analysis found that FBLN1 expression was modulated by miR-1269b, which was downregulated by HG in HK-2 cells. While transfection of miR-1269b reversed FBLN1-mediated EMT in PTECs, miR-1269b inhibitor modulated the phenotype of PTECs toward mesenchymal type under normal glucose (NG) condition. Most importantly, urinary FBLN1 and exosomal miR-1269b levels were correlated with the severity of kidney injury in type 2 diabetic patients.Conclusion: This study demonstrated the communication within PTECs through exosome transmission in an autocrine pattern. MiR-1269b–FBLN1 epigenetic regulatory network could be a potential therapeutic strategy to prevent the progression of DN.

Evaluation of urinary TNF-α and KIM-1 biomarkers in T2DM in Upper Egypt

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Magdy EL Sharkawy ◽  
Samir K Abdul-Hamid ◽  
Tarek T Elmelegy ◽  
Mohammed F Adawy
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Clinical Syndrome ◽  
Diabetic Patients ◽  
University Hospitals ◽  
Type 2 Diabetic Patients ◽  
Cross Sectional ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background Diabetes mellitus (DM) is the most frequent cause of chronic kidney failure in both developed and developing countries. Diabetic nephropathy, is a clinical syndrome characterized by albuminuria (>300 mg/day) with permanent and irreversible decrease in glomerular filtration rate (GFR). Aim of the Work To study the role of urinary TNF-α and urine KIM-1 in type 2 diabetic patients as predictors of DN comparative with albuminuria. Patients and Methods This is a cross-sectional study which include 90 type-2 diabetic patients and 30 controls selected from the outpatient clinic of Assiut University hospitals. All patients gave an informed consent and approval for the study was obtained from the IRB committee of the Assiut Medical Faculty. The recruited patients were divided into three groups: Normo-albuminuria Group (A) (n = 30): UACR less than 30 mg/gm, Microalbuminuria Group (B) (n = 30): UACR between 30-299 mg/gm and Macro-albuminuria Group (C) (n = 30): UACR equal or more than 300 mg/gm. Assess Urinary TNF-α and urine KIM-1 in comparision with albuminuria. Results Urinary KIM-1 and urinary TNF-α are statically significant with albuminuria in patients in the early stage of diabetic nephropathy (eGFR _60 mL/min/1.73 m2).Also there are statically significance between patients with macroalbuminuria than microalbuminuria. Conclusion The results of this study recommend the use of KIM-1 and TNF-α as good predictors of early detection of development of diabetic nephropathy.

scholarly journals A study of prevalence of microalbuminuria in recently detected type 2 diabetes and its relation to hypertension, dyslipidaemia and obesity

2020 ◽  
Vol 11 (5) ◽  
pp. 38-43
Author(s):  
Shrikrishna V Acharya
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Screening Tool ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Group 2 ◽  
Type 2 Diabetic ◽  
Group 1 ◽  
New Onset

Background: Microalbuminuria is one of the earliest markers of diabetic nephropathy, and if not recognized and treated early it may lead to diabetic nephropathy resulting in chronic renal failure. Aims and Objective: The aim of the current study was to find out the prevalence of microalbuminuria among newly detected Type 2 diabetic patients and also compare prevalence of microalbuminuria in patients with or without hypertension, dyslipidaemia and obesity. Materials and Methods: In this retrospective study, we analysed 90 patients with new onset type 2 diabetes mellitus. We divided the patients into two groups, group 1 with comorbidities like hypertension, dyslipidaemia and obesity (50 patients) and group 2 without comorbidities (40 patients). We analysed urinary microalbumin level in all patients and compared the prevalence of microalbuminuria between group 1 and group 2. Results: In our cohort of 90 patients, urinary microalbuminuria was found in 30 patients (33.3%). When we divided these nephropathy patients to group1 and group 2, we observed that group 1 with comorbidities had higher percentage of nephropathy patients i.e 24 out of 50(48%). Group 2 with 40 patients had only 6 patients with microalbiminuria ie 6 out of 40(15%). Incidence of microalbiminuria was higher in patients with hypertension, dyslipidaemia and obesity. Conclusions: We conclude that incidence of microalbiminuria is much more common in newly diagnosed type 2 diabetes. We also conclude that hypertension, obesity and hypercholesterolemia are risk factors for nephropathy and urinary microalbuminuria appears to be much more sensitive than serum creatinine as screening tool to detect diabetic nephropathy.

scholarly journals CNDP1, NOS3, and MnSOD Polymorphisms as Risk Factors for Diabetic Nephropathy among Type 2 Diabetic Patients in Malaysia

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mohd Jokha Yahya ◽  
Patimah Binti Ismail ◽  
Norshariza Binti Nordin ◽  
Abdah Binti Md Akim ◽  
Wan Shaariah Binti Md Yusuf ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Manganese Superoxide Dismutase ◽  
Multiplicative Model ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic ◽  
Mode Of Inheritance

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of nephropathy. The aim of this study was to investigate the association of a genetic polymorphism of carnosinase (CNDP1-D18S880and -rs2346061), endothelial nitric oxide synthase (NOS3-rs1799983), and manganese superoxide dismutase (MnSOD-rs4880) genes with the development of diabetic nephropathy among Malaysian type 2 diabetic patients. A case-control association study was performed using 652 T2DM patients comprising 227 Malays (without nephropathy = 96 and nephropathy = 131), 203 Chinese (without nephropathy = 95 and nephropathy = 108), and 222 Indians (without nephropathy = 136 and nephropathy = 86). DNA sequencing was performed for theD18S880ofCNDP1, while the rest were tested using DNA Sequenom MassARRAY to identify the polymorphisms. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models, and the best mode of inheritance was chosen based on the leastpvalue. Thers2346061ofCNDP1was significantly associated with diabetic nephropathy among the Indians only with OR = 1.94 and 95% CI = (1.76–3.20) and fitted best the multiplicative model, whileD18S880was associated among all the three major races with the Malays having the strongest association with OR = 2.46 and 95% CI = (1.48–4.10), Chinese with OR = 2.26 and 95% CI = (1.34–3.83), and Indians with OR = 1.77 and 95% CI = (1.18–2.65) in the genotypic multiplicative model. The best mode of inheritance for bothMnSODandNOS3was the additive model. ForMnSOD-rs4880, the Chinese had OR = 2.8 and 95% CI = (0.53–14.94), Indians had OR = 2.4 and 95% CI = (0.69–2.84), and Malays had OR = 2.16 and 95% CI = (0.54–8.65), while forNOS3-rs1799983, the Indians had the highest risk with OR = 3.16 and 95% CI = (0.52–17.56), followed by the Chinese with OR = 3.55 and 95% CI = (0.36–35.03) and the Malays with OR = 2.89 and 95% CI = (0.29–28.32). The four oxidative stress-related polymorphisms have significant effects on the development of nephropathy in type 2 diabetes patients. The genes may, therefore, be considered as risk factors for Malaysian subjects who are predisposed to T2DM nephropathy.

Sign in / Sign up

Export Citation Format

Share Document