Prognostic value of plasminogen activator inhibitor type 1 mRNA in microdissected glomeruli from transplanted kidneys

Background. Plasminogen activator inhibitor type 1 (PAI-1) exerts antifibri nolytic and profibrotic activities. Inside the glomerulus, PAI-1 is mainly synthesized by mesangial cells. We hypothesized that thrombin, via its rece ptor protease activated receptor type 1 (PAR-1), present on the membrane of glomerular cells, is an important mediator of PAI-1 synthesis. Methods. Using the technique of Peten et al., we microdissected the glomeru li of 23 kidney transplanted patients admitted in our department from 1993 to 1997, and we followed-up these patients for up to 5 years, with sometime s iterative renal biopsies. With this technique, we also microdissected the glomeruli of three patients who have had a nephrectomy for cancer (control patients). We investigated mRNA expression of the PAI-1, the thrombin rece ptor PAR-1, the alpha2 chain of type IV (alpha2 IV) collagen, and of a hous ekeeping gene (cyclophilin) by reverse transcription-polymerase chain react ion. The results were correlated with the renal function and the histologic al findings classified into acute rejection (9 biopsies), chronic rejection (22 biopsies), or normal (8 biopsies). Results. A significant up-regulation of PAI-1 and a2 IV collagen mRNA was o bserved in acute rejection (P<0.05) when compared to norm al kidneys. A pos itive correlation exists between <alpha>2 IV collagen mRNA level and the de gree of cellular infiltration. A negative correlation was found between the level of mRNA of PAR-1 and the degree of vascular thrombosis (P=0.005) and glomerulosclerosis (P=0.04). A positive correlation was found between the degradation of renal function and the mRNA level of PAI-1 at the time of th e renal biopsy (P<0.05). Conclusions. These results suggest that glomerular PAI-1 mRNA may be predic tive of the long-term renal graft function.