ABSTRACT
MicroRNAs (miRNAs) have already been documented to function in diabetic nephropathy (DN), yet little research has focused on the role of miR-98 in this disease. Here, we discuss the mechanism of miR-98 on the renal fibrosis in DN. Recombinant adeno-associated virus carrying miR-98 inhibitor or Nedd4L overexpression plasmid was injected into DN modeled rats to explore their roles in DN. Renal tubular epithelial cell injury models (NRK-52E cells) were induced by high glucose (HG). HG-treated NRK-52E cells were transfected with miR-98 inhibitor or Nedd4L overexpression plasmid for further verification. MiR-98 was upregulated, Nedd4L was downregulated and TGF-ß/Smad2/3 signaling was activated in kidney tissues of DN rats and HG-treated NRK-52E cells. miR-98 targeted Nedd4L mRNA 3'UTR. MiR-98 depletion and Nedd4L overexpression inactivated TGF-ß/Smad2/3 signaling pathway, alleviated pathological damage and fibrosis, ameliorated inflammation, and depressed cell apoptosis of kidney tissues of DN rats. MiR-98 depletion and Nedd4L overexpression inactivated TGF-ß/Smad2/3 signaling pathway, strengthened viability, and limited apoptosis of HG-treated renal tubular epithelial cells. Nedd4L overexpression reversed the effect of up-regulating miR-98 on DN rats and HG-treated renal tubular epithelial cells. Altogether, we find that miR-98 is upregulated in kidney tissues of DN rats, and miR-98 diminution and Nedd4L elevation attenuate renal fibrosis through inactivation of the TGF-ß/Smad2/3 pathway, which provides a novel therapy for DN.
Subject(s)
Diabetic Nephropathies/metabolism , Kidney/pathology , MicroRNAs/metabolism , Nedd4 Ubiquitin Protein Ligases/metabolism , Signal Transduction/genetics , Smad2 Protein/metabolism , Transforming Growth Factor beta/metabolism , Animals , Apoptosis/genetics , Cell Line , Cell Survival/genetics , Diabetic Nephropathies/genetics , Disease Models, Animal , Down-Regulation/genetics , Epithelial Cells/metabolism , Fibrosis , Kidney Tubules/cytology , MicroRNAs/genetics , Nedd4 Ubiquitin Protein Ligases/genetics , Rats , Rats, Sprague-Dawley , Smad3 Protein , Transfection , Up-Regulation/geneticsABSTRACT
BACKGROUND: This study aims to observe the outcome and safety of umbilical cord-mesenchymal stem cell (UC-MSC) treatment for continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: A total of 24 CAPD patients, who underwent UC-MSC treatment from June 2011 to December 2012, were selected for this study. These patients were followed up until June 2015. RESULTS: Results revealed a significant increase in hemoglobin, erythropoietin and albumin levels, a decrease in C-reactive protein levels, and marked improvement in cystatin C and urine volume within three months after UC-MSC transplantation; and the difference was statistically significant (P<0.05). However, the difference in residual glomerular filtration rate, serum creatinine, peritoneal KT/V and remnant kidney KT/V was not statistically significant (P>0.05). CONCLUSIONS: Clinical indicators of patients with CAPD can be partially improved through UC-MSC treatment.
