Angiotensinogen Expression Is Enhanced in the Progression of Glomerular Disease英文文献资料.docVIP

International Journal of Clinical Medicine, 2011, 2, 378-387 doi:10.4236/ijcm.2011.24064 Published Online September 2011 (http://www.SciRP.org/journal/ijcm) Angiotensinogen Expression Is Enhanced in the Progression of Glomerular Disease Maki Urushihara, Hiroyuki Kobori Department of Physiology, and Hypertension and Renal Center of Excellence Tulane University Health Sciences Center, New Or- leans, USA. Email: murushih@ Received April 11 , 2011; reised May 13 , 2011; accepted July 17 2011. th rd th ABSTRACT Intrarenal renin-angiotensin system (RAS) activation plays a critical role in the development and progression of renal injury. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by multiple independent mechanisms. Angiotensinogen (AGT) is the only known substrate for renin that is a rate-limiting enzyme of the RAS. Recently, enhanced intrarenal AGT levels have been shown to reflect the intrarenal RAS status in hypertension, chronic glomerular disease and diabetic nephropathy. In this review, we focus on AGT expression of the diseased glomeruli in the progression of glomerular disease. An anti-glomerular basement membrane nephritis rat model devel- oped progressive proteinuria and glomerular crescent formation, accompanied by increased macrophage infiltration and glomerular expression of AGT and Ang II. The addition of Ang II type 1 receptor blocker to CC-chemokine recap- tor 2 antagonist markedly attenuated the induction of macrophage infiltration, AGT and Ang II, and reduced glomeru- lar crescent formation. Next, the levels of glomerular AGT expression and marker of reactive oxygen species in Zucker diabetic fatty (ZDF) obese rats were higher than those in ZDF lean rats. Hydrogen peroxide (H2O2) induced an in- crease in the AGT expression in primary rat