Inhibition Of CTGF And ECM Expression In Human Renal Proximal Tubular Epithelial Cells By PBSHH1 Plasmid Vector Mediated CTGF ShRNA

Renal tubulointerstitial fibrosis as a significant index to the chronic progression of various renal diseases and a common characteristic of the end stage renal disease(ESRD) is a more consistent predictor of functional impairment than glomerular damage.The major pathological changes of tubulointerstitial fibrosis is the accumulation of matrix protein in renal interstitium due to the over-production and blunted degradation of extracellular matrix (ECM).Although the mechanisms of tubulointerstitial fibrosis have not been completely clarified, cytokine network is the focus all along. Transforming growth factor-β₁(TGF-β₁), an important factor of fibrosis, can promote tubular epithelial cell transdifferentiation towards myofibroblast, enhance the synthesis of ECM proteins and promotes ECM accumulation by increasing the production of protease inhibitors such as plasminogen activator inhibitor-1 (PAI-1) and by decreasing the activity of proteases such as matrix metalloproteinases. Connective tissue growth factor (CTGF) as the downstream factor of TGF-β₁ is thought to mediate the latter's profibrotic effects by modulating fibroblast cell growth and ECM protein synthesis.CTGF mRNA overexpression was found in tubular epithelial cells and interstitial cells at sites of chronic interstitial damage. In the remnant kidney of the subtotal nephrectomy (SNx) model and in the kidneys with ureteral obstruction, tubular CTGF was shown to be expressed in response to renal interstitial fibrosis. These findings strongly suggest that renal interstitial fibrogenesis is mediated by CTGF that is expressed in the tubular epithelial cells. Thus down-...