Increased glomerular Vwf after kidney irradiation is not due to increased biosynthesis or endothelial cell proliferation

Irradiation of the kidney induces dose-dependent, progressive renal functio nal impairment, which is partly mediated by vascular damage. It has previou sly been demonstrated that reduced renal function is preceded by an increas ed amount of von Willebrand factor (Vwf) in the glomerulus, The underlying mechanism and significance of this observation are unknown but, since it is an important mediator of platelet adhesion, Vwf in increased amounts could be implicated in glomerular thrombosis, resulting in impairment of renal f unction. Increased Vwf could be the result of increased biosynthesis by end othelial cells, or from increased numbers of endothelial tells after compen satory proliferation induced by irradiation, or it could be secondary to ot her events. In the present study, expression levels of mRNA for glomerular Vwf and glomerular cell proliferation rates were measured in control mouse kidneys and after irradiation with a single dose of 16 Gy. There were no si gnificant changes in mRNA ratios for Vwf/beta -actin at 10 to 30 weeks afte r irradiation compared with unirradiated samples, whereas increased amounts of Vwf protein were seen in the glomeruli at these times. Labeling studies with IdU or staining for Ki67 demonstrated that glomerular proliferation w as increased from 10 to 30 weeks after irradiation. Despite the increased p roliferation rates, there was an absence of glomerular hyperplasia and no i ncrease in the endothelial cell surface coverage in the glomeruli, Staining with antibodies against smooth muscle actin (SMA alpha) revealed that the observed proliferation mainly involved mesangial cells. These results indic ate that the increased presence of glomerular Vwf after irradiation is not due to an increased number of endothelial cells per glomerulus, or to an in creased production of Vwf It is presumably secondary to other events, such as increased release of Vwf by damaged endothelial cells or entrapment of V wf in the irradiated mesangial matrix. (C) 2001 by Radiation Research Socie ty.