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

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

Research output: Contribution to journalArticle

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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 2008
Externally publishedYes

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Heme Oxygenase-1
Epithelial-Mesenchymal Transition
Fibrosis
Kidney
Ureteral Obstruction
Hydronephrosis
Kidney Diseases
Heme Oxygenase 1 Deficiency
Smooth Muscle
Actins
Epithelial Cells
Macrophages
Inflammation

ASJC Scopus subject areas

  • Nephrology
  • Medicine(all)

Cite this

Heme oxygenase-1 deficiency promotes epithelial-mesenchymal transition and renal fibrosis. / Kie, Jeong Hae; Kapturczak, Matthias H.; Traylor, Amie; Agarwal, Anupam; Hill-kapturczak, Nathalie S.

In: Journal of the American Society of Nephrology, Vol. 19, No. 9, 09.2008, p. 1681-1691.

Research output: Contribution to journalArticle

Kie, Jeong Hae ; Kapturczak, Matthias H. ; Traylor, Amie ; Agarwal, Anupam ; Hill-kapturczak, Nathalie S. / Heme oxygenase-1 deficiency promotes epithelial-mesenchymal transition and renal fibrosis. In: Journal of the American Society of Nephrology. 2008 ; Vol. 19, No. 9. pp. 1681-1691.
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