A mutant, noninhibitory plasminogen activator inhibitor type 1 decreases matrix accumulation in experimental glomerulonephritis

Effects of Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 in Radiation-Induced Intestinal Injury

“…The role of vitronectin in radiation damage has never been investigated, and drugs capable of inhibiting vitronectin-bound PAI-1 are, therefore, an attractive perspective of our study. For example, by competing with endogenous PAI-1, a mutant noninhibitory PAI-1 able to bind vitronectin was described to reduce glomerulosclerosis (27). Moreover, one may not exclude a limited beneficial action of PAI-039 in a model of very severe radiation injury.…”

“…Further investigations are needed to understand the precise mechanism for the role of PAI-1 in radiation injury and could give fundamental information for more precisely monitoring PAI-1 inhibition. Other strategies to reduce PAI-1 activity are now available and should be tested with this model of radiation-induced intestinal damage (27,(33)(34)(35).…”

The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases

“…72 expression of a mutant, noninhibitory form of Pai-1 decreased matrix accumulation in experimental glomerulonephritis. 73 the mechanisms of the profibrotic actions of Pai-1 initially seemed obvious. as a serine protease inhibitor, Pai-1 was thought to lead to accumulation of eCm at fibrotic sites by decreasing the activity of plasminogen activator, plasmin, and mmPs and thereby impairing the turnover and degradation of eCm.…”

Progression in Chronic Kidney Disease

“…PAI-1-deficient mice develop less severe renal fibrosis after ureteral obstruction while PAI-1 overexpressing mice develop worse fibrosis (Fig 4). 20,59 Other experimental observations that establish PAI-1 as an important mediator of progressive kidney disease include the protective effects of a PAI-1 competitive inhibitor 60 and associations between reduced PAI-1 levels and the renoprotective effects of angiotensin II inhibition 61 and enhanced PAI-1 accumulation and fibrosis severity in mice lacking uPAR, the receptor that mediates PAI-1 degradation. 22 PAI-1 has a strong affinity for vitronectin, an extracellular matrix protein that accumulates in the interstitium of chronically damaged kidneys.…”