Heme Oxygenase-1 Modulates Mesangial Cell Proliferation by P21^Waf1 Upregulation

Abstract

Mesangial cell (MC) proliferation is a hallmark of many progressive renal diseases. Heme oxygenase-1 (HO-1) has been shown to have an anti-proliferative effect on vascular smooth muscle cells. In the present study, we evaluated the role of HO-1 on MC proliferation and the involved molecular mechanism. Both epidermal growth factor (EGF) and hepatocyte growth factor (HGF) not only enhanced mesangial cell HO-1 expression but also stimulated proliferation of MCs. Interestingly, inhibition of HO-1 induction (by zinc protoporphyrin, ZnP) was associated with an accelerated mitogenic response to EGF and HGF in MCs. Induction of HO-1 was associated with enhanced mesangial cell p21 expression. On the other hand, hemoglobin and ZnP inhibited mesangial cell p21 expression. It appears that the effect of HO-1 on MC growth may be mediated through upregulation of p21 expression.

Keywords:

• heme oxygenase-1
• hemin
• mesangial cells
• p21

ACKNOWLEDGMENT

This work was supported by grant RO1 DK 083931 from the National Institutes of Health, Bethesda, Md.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.