Induction of heme oxygenase-1 modulates the profibrotic effects of transforming growth factor-beta in human renal tubular epithelial cells

A. Mark, T. Hock, M. H. Kapturczak, A. Agarwal, N. Hill-Kapturczak

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Transforming growth factor-beta (TGF-beta) is implicated in a variety of kidney diseases where it promotes extracellular matrix (ECM) deposition and pro-inflammatory events, but it also stabilizes and attenuates tissue injury through the activation of cytoprotective proteins, including heme oxygenase-1 (HO-1). HO-1 catalyzes the conversion of heme into carbon monoxide (CO), iron, and biliverdin, which is subsequently converted to bilirubin. The beneficial effects of HO-1 induction include decreasing pro-oxidants (heme), increasing anti-oxidants (biliverdin and bilirubin), and producing a vasodilator with anti-apoptotic and anti-inflammatory properties (CO). The reaction products of HO-1 may also have antifibrogenic properties. The purpose of this study is to explore the effects of HO-1 expression and its reaction products on fibronectin, an ECM protein, in the kidney. The results demonstrate that kidneys of HO-1 knockout mice express significantly more fibronectin protein as compared to heterozygote mice. A potent inducer of HO-1, hemin, significantly decreases fibronectin protein with a concomitant increase in HO-1 protein. Cells expressing HO-1, via TGF-beta1 induction, have reduced fibronectin expression. Bilirubin, a product of the heme oxygenase reaction, attenuates TGF-beta1-mediated increases in fibronectin expression. These results indicate that HO-1 induction and activity may modulate the production of ECM components and suggest a potential role for TGF-beta-mediated HO-1 induction in attenuating renal fibrosis.

Original languageEnglish (US)
Pages (from-to)357-362
Number of pages6
JournalCellular and Molecular Biology
Volume51
Issue number4
DOIs
StatePublished - Sep 30 2005
Externally publishedYes

Keywords

  • Bilirubin
  • Extracellular matrix
  • Fibronectin
  • Heme oxygenase-1
  • Transforming growth factor-beta

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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