Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy.
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-beta (TGF-beta), alpha-smooth-muscle actin, glomerular cell 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-beta 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.
Takamatsu
Masanori
M
Department of Pediatrics, The Institute of Health Bioscience, The University of Tokushima Graduate School, Kuramoto-cho-3-chome, Tokushima, Japan.
Urushihara
Maki
M
Kondo
Shuji
S
Shimizu
Maki
M
Morioka
Tetsuo
T
Oite
Takashi
T
Kobori
Hiroyuki
H
Kagami
Shoji
S
D000293:Adolescent; D000447:Aldehydes / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics* / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D002648:Child; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D005922:Glomerulonephritis, IGA / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000473:pathology* / Q000502:physiology*; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
D000447:Aldehydes; D016212:Transforming Growth Factor beta; D014662:Vasoconstrictor Agents; C448740:beta-acaridial; D000808:Angiotensinogen; D000804:Angiotensin II