Statin Inhibits Pressured-Induced Rat Renal Tubular Cell Apoptosis and Tubulointerstitial Fibrosis

Project: A - Government Institutionb - National Science and Technology Council

Project Details

Description

Statins are known to reduce the incidence of cardiovascular events and death, and these benefits are mainly caused by their lipid-lowering effects. Recently, statins has been reported to activate PPAR and PPAR via COX-2-dependent pathway. In our previous study, the activation of PPAR is capable of protecting rat renal tubular cells from gentamicin-induced apoptosis. Statines are supposed to have potential for renal therapy. Recently, many studies have revealed that the pressure force is an important mechanisms contributing to the induction and progression of tubulo-interstitial fibrogenesis in diabetic nephropathy and obstructive uropathy. In this project, we will clarify whether statins have the capacity to protect renal tubular cell against pressure-induced injury and to examine their underlying mechanisms. We will establish an in vitro pressure system to mimic diabetic nephrosis and the UUO model, and study the molecular mechanisms of statin protection effects in rat renal tubular cells (NRK-52E). We also develope in vivo models to investigate the protective effects of statin on diabetic mice and UUO model. The specific aims of this project are listed as below: 1. Establish the in vitro pressure-induced model and identify the pressure-induced injury in rat renal tubular cells. 2. Reveal the protective effect of statins on rat renal tubular cells treated with high pressure. 3. Reveal the molecular mechanisms in the protective effect of statins against pressure-induced injury, especially focusing on COX-2/PPARs pathway. 4. Confirm the protective mechanism of statins in rat UUO model and diabetes mice. This project will reveal the therapeutic potential of statins for diabetic nephrosis and renal fibrosis.
StatusFinished
Effective start/end date8/1/117/31/12

Keywords

  • statins
  • pressure
  • renal tubular cells

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