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Updated: Aug 15, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Prognostic value of plasminogen activator inhibitor type 1 mRNA in microdissected glomeruli from transplanted kidneys
F Delarue1, A Hertig, C Alberti
1Département de Néphrologie A, Inserm U489, Association Claude Bernard, Hôpital Tenon, Paris, France.
Background:
Plasminogen activator inhibitor type 1 (PAI-1) exerts antifibrinolytic and profibrotic activities. Inside the glomerulus, PAI-1 is mainly synthesized by mesangial cells. We hypothesized that thrombin, via its receptor 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 glomeruli 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 sometimes 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 receptor PAR-1, the alpha2 chain of type IV (alpha2 IV) collagen, and of a housekeeping gene (cyclophilin) by reverse transcription-polymerase chain reaction. The results were correlated with the renal function and the histological findings classified into acute rejection (9 biopsies), chronic rejection (22 biopsies), or normal (8 biopsies).
Results:
A significant up-regulation of PAI-1 and alpha2 IV collagen mRNA was observed in acute rejection (P<0.05) when compared to normal kidneys. A positive correlation exists between alpha2 IV collagen mRNA level and the degree 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 the renal biopsy (P<0.05).
Conclusions:
These results suggest that glomerular PAI-1 mRNA may be predictive of the long-term renal graft function.
Insights
Glomerular plasminogen activator inhibitor type 1 (PAI-1) mRNA levels may predict long-term kidney graft function. Elevated PAI-1 correlates with acute rejection and declining renal function in transplant patients.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Plasminogen activator inhibitor type 1 (PAI-1) has antifibrinolytic and profibrotic roles, primarily synthesized by glomerular mesangial cells.
- Thrombin, acting through protease-activated receptor type 1 (PAR-1), is hypothesized to mediate PAI-1 synthesis in glomerular cells.
Purpose of the Study:
- To investigate the role of thrombin and its receptor PAR-1 in PAI-1 synthesis within kidney glomeruli.
- To determine if PAI-1 mRNA expression correlates with renal graft rejection and function.
Main Methods:
- Microdissection of glomeruli from kidney transplant patients and control nephrectomy patients.
- Analysis of mRNA expression for PAI-1, PAR-1, alpha2 IV collagen, and cyclophilin using reverse transcription-polymerase chain reaction.
- Correlation of mRNA levels with renal function and histological findings (acute rejection, chronic rejection, normal).
Main Results:
- Significant upregulation of PAI-1 and alpha2 IV collagen mRNA in acute rejection compared to normal kidneys.
- Positive correlation between alpha2 IV collagen mRNA and cellular infiltration.
- Negative correlation between PAR-1 mRNA and vascular thrombosis/glomerulosclerosis.
- Positive correlation between PAI-1 mRNA and degradation of renal function.
Conclusions:
- Glomerular PAI-1 mRNA levels may serve as a predictive marker for long-term kidney graft function.
- These findings highlight PAI-1's potential role in kidney transplant outcomes.
