Heme oxygenase-1 deficiency promotes epithelial-mesenchymal transition and renal fibrosis

Academic Article

Abstract

  • Induction of heme oxygenase-1 (HO-1) is associated with potential antifibrogenic effects. The effects of HO-1 expression on epithelial-mesenchymal transition (EMT), which plays a critical role in the development of renal fibrosis, are unknown. In this study, HO-1-/- mice demonstrated significantly more fibrosis after 7 d of unilateral ureteral obstruction compared with wild-type mice, despite similar degrees of hydronephrosis. The obstructed kidneys of HO-1-/- mice also had greater macrophage infiltration and renal tubular TGF-β1 expression than wild-type mice. In addition, the degree of EMT was more extensive in obstructed HO-1-/- kidneys, as assessed by α-smooth muscle actin and expression of S100A4 in proximal tubular epithelial cells. In vitro studies using proximal tubular cells isolated from HO-1-/- and wild-type kidneys confirmed these observations. In conclusion, HO-1 deficiency is associated with increased fibrosis, tubular TGF-β1 expression, inflammation, and enhanced EMT in obstructive kidney disease. Modulation of the HO-1 pathway may provide a new therapeutic approach to progressive renal diseases. Copyright © 2008 by the American Society of Nephrology.
  • Digital Object Identifier (doi)

    Author List

  • Kie JH; Kapturczak MH; Traylor A; Agarwal A; Hill-Kapturczak N
  • Start Page

  • 1681
  • End Page

  • 1691
  • Volume

  • 19
  • Issue

  • 9