Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of plasminogen activator inhibitor type-1 (PAI-1), a member of the serine protease inhibitor (SERPIN) superfamily that functions to negatively regulate the plasmin-based pericellular proteolytic cascade, was induced early after exposure of growth-arrested normal rat kidney (NRK) cells to serum-containing medium. Increased PAI-1 transcription was rapid (evident within 10 min of serum addition) and involved immediate-early response kinetics. [3H]Thymidine autoradiography was used to map the time frame of PAI-1 expression during a synchronous growth cycle. PAI-1 transcript accumulation peaked in mid-G1 phase (approx. 4-6 h post-stimulation) and declined prior to, or concomitant with, the onset of DNA synthetic phase. Serum increased PAI-1 expression in NRK cells in agarose suspension, as well as monolayer, culture; induction in suspended cells (similar to monolayer culture conditions) also occurred in the presence of cyclohexamide or puromycin. The serum-inductive pathway leading to PAI-1 gene activation is thus functional regardless of adhesive conditions or capacity for de novo protein synthesis. The amplitude of induction and maintenance of expression in later stages of G1, however, were subject to adhesive influences. PAI-1 transcript accumulation at 4 and 8 h post-stimulation in newly adherent cells, moreover, was blocked by puromycin, indicating that both immediate-early and secondary mechanisms regulate PAI-1 mRNA levels during progression of NRK cells through an 'activated' G1 growth phase.
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PMID:Complex regulation of plasminogen activator inhibitor type-1 (PAI-1) gene expression by serum and substrate adhesion. 861 56

Keratinocytes were shown to induce the activation of plasminogen activator resulting in the formation of plasmin and the initiation of proteolysis in vitro. Activation of surface bound plasminogen may localize protease activity in the pericellular microenvironment and play a role in inducing both a conformational change and cell locomotion. Plasmin, however, can induce non-proteolytic effects on certain cell functions in a variety of cell lineages. In the present study we examined the effects of plasmin on keratinocytes with a focus on its role in the process of re-epithelialization, which included studies of cell migration, phagocytic-killing and cell proliferation. Migration of freshly isolated human epidermal keratinocytes was analyzed utilizing the agarose gel assay in the presence of 10% human serum. Plasmin at the concentration of 25 U/I induced a 160% increase in the chemotactic migration of keratinocytes that was completely blocked by the plasmin inhibitor alpha2-antiplasmin (Serpin). In the absence of serum, plasmin also induced a reversible chemotactic migration of HaCaT keratinocytes as determined utilizing the microchemotaxis assay. Dose-response analysis showed a bi-phasic effect of plasmin with a maximum increase of 52% in keratinocyte chemotaxis at a concentration of 25 U/I. HaCaT cells on the other hand, showed no detectable in vitro chemokinesis by plasmin. Phagocytic-killing of Candida albicans by freshly isolated epidermal keratinocytes was enhanced in the presence of 25 U/I plasmin which was also reversible by the addition of Serpin. Spontaneous proliferation of HaCaT keratinocytes as determined by 3H-Thymidine uptake on the other hand, was reduced by 47 and 13% in cultures with 25 U/I plasmin for 24 and 48 h respectively, in a Serpin reversible manner. These data suggest that plasmin-induced chemotactic migration of epidermal keratinocytes is accompanied by enhanced phagocytic-killing coupled with suppression of proliferation of these cells which may facilitate re-epithelialization following skin injury.
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PMID:Plasmin promotes keratinocyte migration and phagocytic-killing accompanied by suppression of cell proliferation which may facilitate re-epithelialization of wound beds. 1555 69