Heme oxygenase-1 modulates mesangial cell proliferation by p21 Waf1 upregulation.
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.
Kumar
Dileep
D
Department of Medicine, North Shore University Hospital Manhasset and Long Island Jewish Medical Center, New Hyde Park, New York, USA.
Bhaskaran
Madhu
M
Alagappan
Lakshmi
L
Tori
Dipti
D
Yadav
Iti
I
Konkimalla
Sridevi
S
Magoon
Sandip
S
Singhal
Pravin C
PC
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D051547:Heme Oxygenase-1 / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D015854:Up-Regulation
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017228:Hepatocyte Growth Factor; D051547:Heme Oxygenase-1