The Inhibitory Effect of siRNAs on The High Glucose-Induced Overexpression of TGF-β1 in Mesangial Cells

Abstract

Diabetic nephropathy is characterized by an expansion of the glomerular mesangium, caused by mesangial cell proliferation and an excessive accumulation of extracellar matrix (ECM) proteins, which eventually leading to glomerulosclerosis. TGF-β1 was found to play an important role in the accumulation of ECM in the kidney. In this study, TGF-β1 RNA interference was used as an effective therapeutic strategy. The inhibitory effect of TGF-β1 small interfering RNAs (siRNAs) on the high glucose-induced overexpression of TGF-β1 in rat mesangial ceys (RMCs). A high levels of glucose induces TGF-β1 mRNA and protein, and TGF-β1 siRNAs reduce the ability of high glucose to stimulate their expression. We also examined the inhibitory effect of TGF-β1 siRNAs on the expression of plasminogen activator inhibitor (PAI)-1 and Collagen Type I which are down-regulators of TGF-β1. The expression of TGF-β1, PAI-1 and Collagen Type I was increased in RMCs that were stimulated by 30 mM glucose. TGF-β1 siRNAs reduces high glucose-induced TGF-β1, PAI-1, and Collagen Type I mRNA and protein expression in a dose-dependent manner. In conclusion, the present study demonstrates that TGF-β1 siRNAs effectively inhibits TGF-β1 mRNA and protein expression in RMCs. These suggest that TGF-β1 siRNAs through RNAi may be a useful tool for developing new therapeutic applications for the treatment of diabetic nephropathy.

Zhenqing recipe alleviates diabetic nephropathy in experimental type 2 diabetic rats through suppression of SREBP-1c

“…Both hyperglycemia and hyperlipidemia have been linked to diabetic complications, especially renal damage (Noh et al, 2006;Jha et al, 2010;Rosario and Prabhakar, 2006). The type 2 diabetic rats in our study demonstrated high blood glucose, high TG and TC than normal control rats.…”

“…The increased renal lipid deposition was accompanied by mesangial expansion and further resulted in proteinuria and glomerular sclerosis. This process is associated with the increased expression of transforming growth factor -b1 (TGF-b1) (Wang et al, 2005;Proctor et al, 2006), a key factor that regulates mesangial matrix expansion by eliciting synthesis of extracellular matrix components such as fibronectin and collagens (Noh et al, 2006;Sharma et al, 1996).…”

High Carbohydrate Intakes May Predict More Inflammatory Status Than High Fat Intakes in Pre-Menopause Women With Overweight or Obesity: A Cross-Sectional Study

“…In addition, it has been illustrated to induce macrophages proliferation and deposition in adipose tissue of obese mice [3]. TGF-β over-expression along with high carbohydrate consumption was reported to be related to high blood glucose level that leads to stimulated IKK phosphorylation and secretion of NF-κB-mediated pro-in ammatory such as TGF-β [20,21]. In line with the current results an experimental study indicated that in shes with HCDs, TGF-β, TNF-α and IL 1β, NF-κB, and IL-6 increased [21].…”

Small-Nucleic-Acid-Based Therapeutic Strategy Targeting the Transcription Factors Regulating the Vascular Inflammation, Remodeling and Fibrosis in Atherosclerosis

“…Based on these obseravations, TGF-β1 RNAi may be a feasible therapeutic option for vascular remodeling and fibrosis. TGF-β1 siRNA effectively reduces high-glucose-induced TGF-β1, PAI-1, and collagen type I mRNA, and protein expression in kidney and liver fibrosis [ 13 , 14 , 15 ], and its application in vascular pathologies deserves further investigation.…”