Abstract
The final pathway for the development of diabetic nephropathy (DN) into chronic renal failure in DN is glomerulosclerosis and tubulointerstitial fibrosis. Renal tubular lesions can occur in the early stage of DN renal injury. Cumulative evidence shows that oxymatrine (OMT) has a variety of biological and pharmacological properties. In recent years, more attention has been paid on the preventive and therapeutic influence of OMT on organ fibrosis. In this experiment, db/db mice were intraperitoneally injected with OMT 120 mg/kg for 8 weeks, and NRK-52E cultured with 30 mmol/L glucose and 0.1 mg/mL OMT for 48-hour. We investigated the relationship between Id2 and Twist in NRK-52E cells and the effect of OMT on the expression of E-cadherin, α-SMA, Fibronectin, and Collagen-IV by Western blot, Real-time PCR, Immunofluorescence, cell transfection, Co-Immunoprecipitation, and Luciferase assays. OMT increased the expression of Id2 but decreased that of Twist under high glucose condition in vitro and in vivo. The promoted recovery of Id2 facilitated its binding to Twist and affected E-cadherin activity inhibiting EMT and the excessive proliferation and abnormal deposition of ECM. In brief, OMT promotes Id2 to reverse EMT and exert anti-fibrotic effect in diabetic renal tubular epithelial cells by binding Id2 to Twist and affecting its transcriptional activation of downstream target genes. Or findings provide a new experimental basis for delaying the progress and for treatment of diabetic renal fibrosis.
Highlights
With the increase in the incidence of diabetes mellitus (DM) each year, diabetic nephropathy (DN), known as diabetic kidney disease (DKD), has become one of its most serious complications
Our previous study showed that after OMT intervention of NRK-52E cells cultured with high glucose, the protein and mRNA levels of α-SMA and fibronectin decreased, while the protein and mRNA of E-cadherin increased, suggesting that OMT can inhibit the occurrence of epithelial–mesenchymal transition (EMT) and improve the degree of renal fibrosis (Liu et al, 2016)
In our in vivo experiments, we selected an animal model of type 2 diabetes, db/db mice, a spontaneous type 2 diabetic mouse caused by a defect in the Leptin receptor gene on chromosome 4 discovered by the Jackson Laboratory in the United States in 1966
Summary
With the increase in the incidence of diabetes mellitus (DM) each year, diabetic nephropathy (DN), known as diabetic kidney disease (DKD), has become one of its most serious complications. Our previous study showed that after OMT intervention of NRK-52E cells cultured with high glucose, the protein and mRNA levels of α-SMA and fibronectin decreased, while the protein and mRNA of E-cadherin increased, suggesting that OMT can inhibit the occurrence of EMT and improve the degree of renal fibrosis (Liu et al, 2016). Twist is a transcription factor belonging to the bHLH family This protein has a basic region that binds to E-box on DNA to form a dimer or heterodimer to regulate gene expression. The present study is of great clinical significance for the rational use of matrine resources and provides new experimental evidence for the treatment of DN, as well as, effective targets for the prevention and treatment of DN
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