Jan 11, 2013

Transforming growth factor-β1 receptor inhibition preserves glomerulotubular integrity during ureteral obstruction in adults but worsens injury in neonatal mice

American Journal of Physiology. Renal Physiology
Carolina I GalarretaRobert L Chevalier


Unilateral ureteral obstruction (UUO), a widely used model of chronic kidney disease and congenital obstructive uropathy, causes proximal tubular injury and formation of atubular glomeruli. Because transforming growth factor-β1 (TGF-β1) is a central regulator of renal injury, neonatal and adult mice were subjected to complete UUO while under general anesthesia and treated with vehicle or ALK5 TGF-β1 receptor inhibitor (IN-1130, 30 mg·kg(-1)·day(-1)). After 14 days, glomerulotubular integrity and proximal tubular mass were determined by morphometry of Lotus tetragonolobus lectin distribution, and the fraction of atubular glomeruli was determined by serial section analysis of randomly selected individual glomeruli. Glomerular area, macrophage infiltration, fibronectin distribution, and interstitial collagen were measured by morphometry. Compared with placebo, inhibition of TGF-β1 by IN-1130 decreased apoptosis and formation of atubular glomeruli, prevented parenchymal loss, increased glomerular area and glomerulotubular integrity, and increased proximal tubule fraction of the adult obstructed kidney parenchyma from 17 to 30% (P < 0.05, respectively). IN-1130 decreased macrophage infiltration and fibronectin and collagen depositio...Continue Reading

  • References37
  • Citations7


  • References37
  • Citations7


Mentioned in this Paper

Recombinant Transforming Growth Factor
Chronic Kidney Insufficiency
Renal Glomerular Disease
Renal Tubule Structure
Lotus Tetragonolobus agglutinin
Both Kidneys
Polycystic Kidney, Autosomal Dominant

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis