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

Jeong Hae Kie, Matthias H. Kapturczak, Amie Traylor, Anupam Agarwal, Nathalie Hill-Kapturczak

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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.

Original languageEnglish (US)
Pages (from-to)1681-1691
Number of pages11
JournalJournal of the American Society of Nephrology
Volume19
Issue number9
DOIs
StatePublished - Sep 1 2008

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ASJC Scopus subject areas

  • Nephrology

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