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

被引：17

作者：

Mark, A ^{[1
]}

Hock, T ^{[1
]}

Kapturczak, MH ^{[1
]}

Agarwal, A ^{[1
]}

Hill-Kapturczak, N ^{[1
]}

机构：

[1] Univ Alabama, Dept Med, Nephrol Res & Training Ctr, Birmingham, AL 35294 USA

来源：

CELLULAR AND MOLECULAR BIOLOGY | 2005年 / 51卷 / 04期

关键词：

bilirubin; extracellular matrix; fibronectin; heme oxygenase-1; transforming growth factor-beta;

D O I：

10.1170/T638

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：357 / 362

页数：6

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