| First Author | Huang Y | Year | 2008 |
| Journal | J Am Soc Nephrol | Volume | 19 |
| Issue | 2 | Pages | 329-38 |
| PubMed ID | 18216319 | Mgi Jnum | J:149930 |
| Mgi Id | MGI:3849382 | Doi | 10.1681/ASN.2007040510 |
| Citation | Huang Y, et al. (2008) A PAI-1 mutant, PAI-1R, slows progression of diabetic nephropathy. J Am Soc Nephrol 19(2):329-38 |
| abstractText | Plasminogen activator inhibitor-1 (PAI-1) has been implicated in renal fibrosis. In vitro, PAI-1 inhibits plasmin generation, and this decreases mesangial extracellular matrix turnover. PAI-1R, a mutant PAI-1, increases glomerular plasmin generation, reverses PAI-1 inhibition of matrix degradation, and reduces disease in experimental glomerulonephritis. This study sought to determine whether short-term administration of PAI-1R could slow the progression of glomerulosclerosis in the db/db mouse, a model of type 2 diabetes in which mesangial matrix accumulation is evident by 20 wk of age. Untreated uninephrectomized db/db mice developed progressive albuminuria and mesangial matrix expansion between weeks 20 and 22, associated with increased renal mRNA encoding alpha1(I) and (IV) collagens and fibronectin. Treatment with PAI-1R prevented these changes without affecting body weight, blood glucose, glycosylated hemoglobin, creatinine, or creatinine clearance; therefore, PAI-1R may prevent progression of glomerulosclerosis in type 2 diabetes. |
