Pediatr Nephrol (2008) 23:1257–1267 DOI 10.1007/s00467-008-0801-6 ORIGINAL ARTICLE Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy Masanori Takamatsu & Maki Urushihara & Shuji Kondo & Maki Shimizu & Tetsuo Morioka & Takashi Oite & Hiroyuki Kobori & Shoji Kagami Received: 14 November 2007 / Revised: 30 January 2008 / Accepted: 18 February 2008 / Published online: 18 April 2008 # The Author(s) 2008 Abstract Enhanced intrarenal renin-angiotensin system (RAS) is implicated in the development and progression of renal injury. To investigate whether angiotensinogen (AGT) expression is involved in glomerular RAS activity and glomerular injury, we examined glomerular AGT expression and its correlation with expression of other RAS components, and levels of glomerular injury in samples from patients with immunoglobulin A nephropathy (IgAN) (23) and minor glomerular abnormalities (MGA) (8). Immunohistochemistry showed that AGT protein was highly expressed by glomerular endothelial cells (GEC) and mesangial cells in nephritic glomeruli of IgAN compared with glomeruli of MGA. Levels of glomerular AGT protein were well correlated with levels of glomerular angiotensin II (ang II), transforming growth factor-β (TGF-β), α-smooth-muscle actin, glomerular cell M. Takamatsu : M. Urushihara : S. Kondo : M. Shimizu : S. Kagami (*) Department of Pediatrics, The Institute of Health Bioscience, The University of Tokushima Graduate School, Kuramoto-cho-3-chome, Tokushima 770-8503, Japan e-mail: kagami@clin.med.tokushima-u.ac.jp T. Morioka : T. Oite Department of Cellular Physiology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan H. Kobori Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA H. Kobori Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA, USA number, and glomerulosclerosis score but not with those of glomerular angiotensin-converting enzyme and ang II type 1 receptor. Real-time polymerase chain reaction (RT-PCR) and Western blot analyses using cultured human GEC indicated that ang II upregulated AGT messenger ribonucleic acid (mRNA) and protein expression in a dose- and time- dependent manner. These data suggest that activated glomerular AGT expression is likely involved in elevated local ang II production and, thereby, may contribute to increased TGF-β production and development of glomerular injury in IgAN. Augmentation of GEC-AGT production with ang II stimulation might drive further glomerular injury in a positive-feedback loop. Keywords Renin-angiotensin system . Transforming growth factor-β . Glomerular endothelial cells . α-smooth muscle actin . Mesangial cells Introduction Clinical and experimental studies have provided considerable evidence for the role of the renin-angiotensin system (RAS) in the development of hypertension and progression of renal diseases [1, 2]. It is now established that all components of the RAS are widely distributed in several tissues, including the kidney [3, 4]. The local RAS in the kidney has several pathophysiologic functions for not only regulating blood pressure but also renal cell growth and production of glomerulosclerosis, which is involved in the development of renal fibrosis [5–8]. Indeed, previous studies have shown beneficial effects of angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin II (ang II) type 1 receptor (AT1R) blocker (ARB) on various renal diseases in rats and humans,