Heme Oxygenase-1 Deficiency Promotes Epithelial-Mesenchymal ... : Journal of the American Society of Nephrology (original) (raw)
BASIC RESEARCH
Heme Oxygenase-1 Deficiency Promotes Epithelial-Mesenchymal Transition and Renal Fibrosis
Kie, Jeong-Hae; Kapturczak, Matthias H.; Traylor, Amie; Agarwal, Anupam; Hill-Kapturczak, Nathalie
Department of Medicine, Division of Nephrology, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, Alabama
Correspondence: Dr. Nathalie Hill-Kapturczak, Division of Nephrology, University of Alabama at Birmingham, 1530 3rd Avenue S., Birmingham, AL 35294. Phone: 205-996-6672; Fax: 205-996-6650; E-mail: [email protected] or Dr. Anupam Agarwal, Division of Nephrology, University of Alabama at Birmingham, 1530 3rd Avenue S., Birmingham, AL 35294. Phone: 205-996-6670; Fax: 205-996-6650; E-mail: [email protected]
Accepted March 20, 2008
Received October 12, 2007
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 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
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