Received October 12, 2007
Accepted on March 20, 2008

BASIC RESEARCH

Heme Oxygenase-1 Deficiency Promotes Epithelial-Mesenchymal Transition and Renal Fibrosis

Department of Medicine, Division of Nephrology, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama

¹ To whom correspondence should be addressed. E-mail: agarwal{at}uab.edu.

	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-1 expression than wild-type mice. In addition, the degree of EMT was more extensive in obstructed HO-1^-/- kidneys, as assessed by -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-1 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.