Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glomerular plasminogen activator inhibitor-1 (PAI-1) steady-state mRNA and bioactivity were increased after the induction of an augmented form of antiglomerular basement membrane (GBM) antibody glomerulonephritis. PAI-1 mRNA expression was noted at 6 h, peaking at 1 day, and although falling thereafter, remained higher than that of the control group through Day 17. PAI-1 mRNA expression correlated with glomerular PAI-1 bioactivity as determined by a functional tissue type plasminogen activator (t-PA) binding assay. Glomerular PAI-1 bioactivity, not detected in controls, increased to 1.4 +/- 0.3 ng/mg of glomerular lysate at 6 h and then decreased to 0.7 +/- 0.1 ng/mg of glomerular lysate by Day 6. The mRNA of the plasminogen activators (urokinase plasminogen activator), t-PA) either remained unchanged or declined through Day 1, with a slight increase in t-PA mRNA at Day 6. Interleukin-1 beta mRNA expression was maximal at 6 h, declining by Day 3. Transforming growth factor beta 1 (TGF-beta 1) mRNA began to increase at Day 1, was maximal at Day 6, and fell only slightly by Day 17. Epidermal growth factor mRNA decreased. The increase in PAI-1 mRNA and bioactivity, possibly induced early by the interleukin-1 beta response and perhaps later by the TGF-beta 1 response, was associated with striking glomerular capillary lumen fibrin accumulations on Day 1, which decreased and appeared to recanalize as the PAI-1 mRNA and bioactivity fell. The glomerular lesion continued to have some fibrin deposits even on Day 17 and, in addition, had changes of thickened GBM, suggestive of the early stages of diffuse glomerulosclerosis. The latter had a temporal relationship with the persisting increase in TGF-beta 1 and PAI-1 mRNA levels. These observations suggest the possibility that inhibition of enzymes capable of remodeling excessive extracellular matrix production may have contributed to the thickened GBM.
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PMID:Dysfunction of glomerular fibrinolysis in experimental antiglomerular basement membrane antibody glomerulonephritis. 832 70

Transforming growth factor beta 1 (TGF-beta1) affects growth plate chondrocytes through Smad-mediated mechanisms and has been shown to increase protein kinase C (PKC). This study determined if PKC mediates the physiological response of rat costochondral growth zone (GC) chondrocytes to TGF-beta1; if the physiological response occurs via type II or type III TGF-beta receptors, and, if so, which receptor mediates the increase in PKC; and the signal transduction pathways involved. Treatment of confluent GC cells with TGF-beta1 stimulated [(3)H]thymidine and [(35)S]sulfate incorporation as well as alkaline phosphatase (ALPase) and PKC specific activities. Inhibition of PKC with chelerythrine, staurosporine, or H-7 caused a dose-dependent decrease in these parameters, indicating that PKC signaling was involved. TGF-beta1-dependent PKC and the physiological response of GC cells to TGF-beta1 was reversed by anti-type II TGF-beta receptor antibody and soluble type II TGF-beta receptor, showing that TGF-beta1 mediates these effects through the type II receptor. The increase in [3H]thymidine incorporation and ALPase specific activity were also regulated by protein kinase A (PKA) signaling, since the effects of TGF-beta1 were partially blocked by the PKA inhibitor H-8. The mechanism of TGF-beta1 activation of PKC is through phospholipase A(2) (PLA(2)) and not through phospholipase C (PLC). Arachidonic acid increased PKC in control cultures and was additive with TGF-beta1. Prostanoids are required, as indomethacin blocked the effect of TGF-beta1, and Cox-1, but not Cox-2, is involved. TGF-beta1 stimulates prostaglandin E(2) (PGE(2)) production and exogenous PGE(2) stimulates PKC, but not as much as TGF-beta1, suggesting that PGE(2) is not sufficient for all of the prostaglandin effect. In contrast, TGF-beta1 was not regulated by diacylglycerol; neither dioctanoylglycerol (DOG) nor inhibition of diacylglycerol kinase with R59022 had an effect. G-proteins mediate TGF-beta1 signaling at different levels in the cascade. TGF-beta1-dependent increases in PGE(2) levels and PKC were augmented by the G protein activator GTP gamma S, whereas inhibition of G-protein activity via GDP beta S, pertussis toxin, or cholera toxin blocked stimulation of PKC by TGF-beta1, indicating that both G(i) and G(s) are involved. Inhibition of PKA with H-8 partially blocked TGF-beta1-dependent PKC, suggesting that PKA inhibition on the physiological response was via PKA regulation of PKC signaling. This indicates that multiple interacting signaling pathways are involved: TGF-beta1 stimulates PLA(2) and prostaglandin release via the action of Cox-1 on arachidonic acid. PGE(2) activates the EP2 receptor, leading to G-protein-dependent activation of PKA. PKA signaling results in increased PKC activity and PKC signaling regulates proliferation, differentiation, and matrix synthesis.
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PMID:Transforming growth factor-beta1 regulation of growth zone chondrocytes is mediated by multiple interacting pathways. 1206 64