Angiotensinogen Expression Is Enhanced in the Progression of Glomerular Disease

Area of Science:

• Nephrology
• Renal Pathophysiology
• Molecular Biology

Background:

• Intrarenal renin-angiotensin system (RAS) activation is crucial in renal injury progression.
• Angiotensinogen (AGT) is the rate-limiting substrate in RAS, and its intrarenal levels indicate RAS status.
• Enhanced intrarenal AGT reflects disease severity in hypertension, chronic glomerular disease, and diabetic nephropathy.

Purpose of the Study:

• To investigate the role of glomerular AGT expression in the progression of glomerular disease.
• To explore the mechanisms regulating AGT expression in diseased glomeruli.

Main Methods:

• Utilized an anti-glomerular basement membrane nephritis rat model to study proteinuria, crescent formation, and macrophage infiltration.
• Administered Angiotensin II type 1 receptor blockers and CC-chemokine receptor 2 antagonists.
• Examined glomerular AGT and reactive oxygen species (ROS) in Zucker diabetic fatty (ZDF) rats.
• Investigated the effect of hydrogen peroxide (H(2)O(2)) on AGT expression in rat mesangial cells, using specific kinase inhibitors.

Main Results:

• The nephritis model showed increased macrophage infiltration and glomerular AGT/Ang II expression.
• Combined blockade of Ang II type 1 receptor and CCR2 attenuated macrophage infiltration, AGT/Ang II induction, and crescent formation.
• ZDF obese rats exhibited higher glomerular AGT and ROS levels than ZDF lean rats.
• H(2)O(2) increased AGT expression in mesangial cells, an effect inhibited by MEK and JNK inhibitors.

Conclusions:

• Enhanced glomerular AGT expression is implicated in intrarenal RAS activation and the development of glomerular disease.
• Targeting AGT or its regulatory pathways may represent a therapeutic approach for glomerular pathologies.
• ROS signaling pathways, specifically involving MEK and JNK, may contribute to AGT upregulation in glomerular disease.