P1845The pro-inflammatory signaling lipid sphingosine-1-phosphate regulates gene and protein expression of both tissue factor and plasminogen activator inhibitor-1 in differentiated fat cells

We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-κB (a pro-inflammatory transcription factor) content in MNC while also reducing the p;asma concentration of NF-κB dependent pro-inflammatory cytokines and adhesion molecules. We have now tested the effect of insulin on the pro-inflammatory transcription factor, early growth response-1 (Egr-1) and plasma concentration of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), two major proteins whose expression is modulated by Egr-1. Insulin was infused at the rate of 2 IU/h in 5% dextrose (100 mL/h) and KCI (8 mmol/h) for 4 h in the fasting state in ten obese subjects. Blood samples were obtained at 0, 2, 4 and 6 h. MNC were isolated and their total homogenates and nuclear fractions were prepared and Egr-1 was measured by electrophoretic mobility shift assay (EMSA). Plasma TF and PAI-1 were assayed by ELISA. There was a significant fall in Egr-1 at 2 (66 ± 14% of basal level) and 4 h (47± 17% of the basal level; P<0.01). PAI-1 levels (basal = 100%) decreased significantly after insulin infusion at 2 h (57 ± 6.7% of the basal level) and at 4 h (58 ± 8.3% of the basal level; P<0.001). Plasma TF levels (basal = 100%) decreased to 76 ± 7.7% of the basal level at 2 h and to 85 ± 10.4% of the basal level at 4 h (P<0.05). Thus, insulin reduces intranuclear Egr-1 and the expression of TF and PAI-1. These data provide further evidence that insulin has an anti-inflammatory effect including the inhibition of TF and PAI-1 expression. These effects suggest a potential beneficial effect of insulin in thrombin formation and fibrinolysis in atherothrombosis.

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Notoginsenoside R1 counteracts the induction of plasminogen activator inhibitor-1 and tissue factor in response to endotoxin stimulation in vitro and in vivo

Fibrinolysis and Proteolysis ◽

10.1016/0268-9499(94)90620-3 ◽

1994 ◽

Vol 8 ◽

pp. 119

Author(s):

W.J. Zhang ◽

J.I. Woita ◽

B.R.I. Binder

Keyword(s):

Tissue Factor ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor

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Regulation by Nitric Oxide of Endotoxin-Induced Tissue Factor and Plasminogen Activator Inhibitor-1 in Endothelial Cells

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613355 ◽

2002 ◽

Vol 88 (12) ◽

pp. 1060-1065 ◽

Cited By ~ 19

Author(s):

Ana Pérez-Ruiz ◽

Ramón Montes ◽

Francisco Velasco ◽

Chary López-Pedrera ◽

José Páramo ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Tissue Factor ◽

Plasminogen Activator ◽

Umbilical Vein ◽

Plasminogen Activator Inhibitor ◽

No Production ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor ◽

Pai 1

SummaryThe increase in nitric oxide (NO) production in lipopolysaccharide (LPS)-induced sepsis is thought to contribute to the development of shock. However, NO could also play an antithrombotic role. Little is known about the modulating effect of NO on the endothelial overexpression and production of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) occurring in endotoxemia. We analyzed the effect of N(G)-nitro-L-arginine-methyl-ester (L-NAME), an inhibitor of NO synthases, and S-nitroso-N-acetyl-D,L-penicillamine (SNAP), a NO donor, on the expression and synthesis of TF and PAI-1 by LPS-challenged human umbilical vein endothelial cells (HUVEC): L-NAME enhanced the increase in TF mRNA and antigen levels (P <0.05) observed in LPS-treated HUVEC; SNAP down-regulated the LPSinduced TF increment (p <0.05). However, no effects of NO on regulation of the LPS-dependent increase in PAI-1 could be seen. Thus, NO could play an antithrombotic role in sepsis by down-regulating the endothelial overexpression and production of TF.

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PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) IS REGULATED BY iNOS DURING HEMORRHAGIC SHOCK AND IS INVOLVED IN PRO-INFLAMMATORY SIGNALING AND TISSUE INJURY.

Shock ◽

10.1097/00024382-200306001-00150 ◽

2003 ◽

Vol 19 (Supplement) ◽

pp. 51

Author(s):

Claudio Lagoa ◽

Franck Lhuillier ◽

Carol McCloskey ◽

Yoram Vodovotz ◽

Wendy Mars ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Plasminogen Activator ◽

Tissue Injury ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Inflammatory Signaling ◽

Activator Inhibitor ◽

Pai 1

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BAY11‑7082 inhibits the expression of tissue factor and plasminogen activator inhibitor‑1 in type‑II alveolar epithelial cells following TNF‑α stimulation via the NF‑κB pathway

Experimental and Therapeutic Medicine ◽

10.3892/etm.2020.9608 ◽

2020 ◽

Vol 21 (2) ◽

Author(s):

Yumei Cheng ◽

Bo Liu ◽

Hong Qian ◽

Huilin Yang ◽

Yahui Wang ◽

...

Keyword(s):

Epithelial Cells ◽

Tissue Factor ◽

Plasminogen Activator ◽

Plasminogen Activator Inhibitor ◽

Alveolar Epithelial Cells ◽

Type Ii ◽

Plasminogen Activator Inhibitor 1 ◽

Alveolar Epithelial ◽

Tnf Α ◽

Activator Inhibitor

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Sphingosine-1-Phosphate Is a Possible Fibrogenic Factor in Gluteal Muscle Fibrosis

Physiological Research ◽

10.33549/physiolres.932441 ◽

2013 ◽

pp. 691-699 ◽

Cited By ~ 7

Author(s):

C. G. ZHAO ◽

J. QIN ◽

X. J. HE ◽

Y. C. GUAN ◽

Y. JIA ◽

...

Keyword(s):

Growth Factor ◽

Plasminogen Activator ◽

Transforming Growth Factor ◽

Plasminogen Activator Inhibitor ◽

Transforming Growth Factor Β1 ◽

Dependent Manner ◽

Plasminogen Activator Inhibitor 1 ◽

Gluteal Muscle ◽

Sphingosine 1 Phosphate ◽

Activator Inhibitor

Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles due to multiple etiologies. The main pathologic process is characterized by proliferation of fibroblasts and excessive accumulation of collagen in the extracellular matrix of the muscle. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and has been reported to be associated with various fibrotic diseases. However, the role of S1P in GMC remains unknown. Here in this article, High-performance liquid chromatography and immunohistochemistry were applied to evaluate S1P localization and expression in clinical samples from patients with GMC, Quantitative real time PCR, Western blot, and enzyme-linked immunosorbent assay were used to explore the link between transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor-1 (PAI-1) and S1P. The results showed that S1P was enhanced in contraction band (CB) tissues. Studies using the cell proliferation and transformation assay indicated that exogenous S1P stimulated CB fibroblast proliferation in a time-dependent manner and in higher concentration also in a dose-dependent manner. Furthermore, we demonstrated that S1P not only promoted collagen type I production, but also up-regulated mRNA and protein expression of transforming growth factor-β1 and plasminogen activator inhibitor-1. These findings suggest that S1P may regulate increased synthesis of collagen and other fibrogenic factors, and significantly contributes to the process of gluteal muscle scarring in patients with GMC.

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