PAI-1, fibrosis, and the elusive provisional fibrin matrix
نویسندگان
چکیده
منابع مشابه
PAI-1, fibrosis, and the elusive provisional fibrin matrix.
Whether induced surgically or by hypertension, infections, extreme heat, or caustic chemicals, tissue injury invariably leads to vasodilatation, with subsequent leakage of plasma proteins into the connective tissues, rapid activation of the coagulation cascade, and deposition of fibrin. A central paradigm in the field is that the fibrin is organized into a “provisional fibrin matrix,” which act...
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Substantial evidence demonstrates a link of increased plasminogen activator inhibitor-1 (PAI-1) and glomerulosclerosis and kidney fibrosis, providing a novel therapeutic option for prevention and treatment of chronic kidney diseases. Several mechanisms contributing to increased PAI-1 will be addressed, including classic key profibrotic factors such as the renin-angiotensin-system (RAS) and tran...
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A delicate balance exists between ECM synthesis and degradation such that interruption of the corresponding pathways results in increased plasminogen activator inhibitor-1 (PAI-1), pathological matrix accumulation, and glomerulosclerosis. A new study demonstrates that therapy with a mutant PAI-1 increases matrix turnover and reduces glomerulosclerosis by competing with endogenous PAI-1, suggest...
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The present study compared the activities of recombinant tissue-type plasminogen activator (t-PA) and a plasminogen activator inhibitor-1 (PAI-1)-resistant variant t-PA (Kt-PA, KHRR 296-299 AAAA) in preventing renal fibrin deposition in rabbits with elevated PAI-1 activity. In this model, all rabbits were infused with endotoxin (10 micrograms/kg), followed by initiation of thrombin (130 U/kg) 4...
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After injury, the wound space is filled with a fibrin/fibronectin clot containing growth factors released by platelets and monocytes. In response to these factors, fibroblasts migrate into the fibrin clot and contribute to the formation of granulation tissue. The functional mechanisms allowing fibroblasts to leave the collagenous matrix of normal connective tissue and invade the provisional mat...
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ژورنال
عنوان ژورنال: Journal of Clinical Investigation
سال: 2000
ISSN: 0021-9738
DOI: 10.1172/jci11765