Related Experiment Video

Updated: Jun 5, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
10:31

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice

Published on: May 2, 2025

Renal (pro)renin receptor contributes to development of diabetic kidney disease through transforming growth

Jiqian Huang1, Luis C Matavelli, Helmy M Siragy

  • 1Department of Medicine, Division of Endocrinology & Metabolism, University of Virginia Health System, Charlottesville, VA 22908-1409, USA.

Clinical and Experimental Pharmacology & Physiology
|January 27, 2011
PubMed

Insights

The (pro)renin receptor (PRR) pathway exacerbates diabetic kidney disease by increasing transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) signaling. Blocking PRR reduces these effects, offering a potential therapeutic target for diabetic nephropathy.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetic nephropathy is characterized by renal fibrosis, involving transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF).
  • The (pro)renin receptor (PRR) is upregulated in diabetic kidneys, suggesting a role in disease pathogenesis.
  • Hyperglycemia is a key driver of diabetic kidney disease, potentially influencing PRR and downstream signaling.

Purpose of the Study:

  • To investigate the role of PRR in high glucose-induced TGF-β1 and CTGF signaling in diabetic kidney disease.
  • To determine if PRR blockade can attenuate the development of diabetic kidney disease.
  • To elucidate the relationship between PRR, angiotensin AT1 receptor, and TGF-β1/CTGF pathways.

Main Methods:

  • In vivo studies using streptozotocin (STZ)-induced diabetic rats treated with PRR blockade (handle region peptide - HRP) or valsartan.
  • In vitro studies using rat mesangial cells (RMC) exposed to high glucose and treated with HRP, PRR siRNA, or valsartan.
  • Assessment of PRR, TGF-β1, and CTGF expression, as well as PRR phosphorylation, in kidney tissues and RMC.

Main Results:

  • PRR, TGF-β1, and CTGF were upregulated in diabetic kidneys and high glucose-treated RMC.
  • High glucose induced PRR phosphorylation, which was inhibited by HRP, valsartan, and PRR siRNA.
  • PRR blockade (HRP or siRNA) and valsartan significantly reduced renal and RMC TGF-β1 and CTGF expression.

Conclusions:

  • PRR activation contributes to diabetic kidney disease by enhancing TGF-β1-CTGF signaling.
  • Blocking PRR or the angiotensin AT1 receptor can attenuate TGF-β1 and CTGF upregulation in diabetes.
  • PRR represents a potential therapeutic target for managing diabetic nephropathy.

Related Concept Videos

Diabetic Nephropathy01:28

Diabetic Nephropathy

Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar...
Renal Corpuscle01:20

Renal Corpuscle

The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous capillaries...
Introduction to Urinary System01:13

Introduction to Urinary System

The urinary system consists of two kidneys, two ureters, the urinary bladder, and the urethra.
The kidneys are bean-shaped organs located in the retroperitoneal space, on either side of the vertebral column, between the T12 and L3 vertebrae. They are partially protected by the rib cage and surrounded by perirenal fat, which provides cushioning. They are responsible for urine formation and play critical roles in regulating blood pressure, electrolyte levels, and hormone production. The ureters...
Hormonal Regulation01:33

Hormonal Regulation

The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Diabetic Retinopathy01:27

Diabetic Retinopathy

DefinitionDiabetic retinopathy is a microvascular complication of diabetes affecting the retinal blood vessels.Risk FactorsDiabetic retinopathy is present in almost all individuals with type 1 diabetes and more than 60% of those with type 2 diabetes after two decades of disease.The risk increases with poor glycemic control, hypertension, dyslipidemia, smoking, pregnancy, and puberty.Although cataracts and glaucoma are also more frequent in people with diabetes, retinopathy remains the leading...