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

被引：86

作者：

Kie, Jeong-Hae ^{[1
]}

Kapturczak, Matthias H. ^{[1
]}

Traylor, Amie ^{[1
]}

Agarwal, Anupam ^{[1
]}

Hill-Kapturczak, Nathalie ^{[1
]}

机构：

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

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2008年 / 19卷 / 09期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1681/ASN.2007101099

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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-beta 1 expression than wild-type mice. In addition, the degree of EMT was more extensive in obstructed HO-1(-/-) kidneys, as assessed by a-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-beta 1 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.

引用

页码：1681 / 1691

页数：11

共 60 条

[1] Retrovirus-mediated human heme oxygenase-1 (HO-1) gene transfer into rat endothelial cells:: the effect of HO-1 inducers on the expression of cytokines [J].