Thrombin regulation of tissue-type plasminogen activator synthesis in cultured human fetal lung fibroblasts

Hayakawa, Yumiko; Tazawa, Shigeki; Ishikawa, T.; Niiya, Kenji; Sakuragawa, Nobuo

doi:10.1016/0049-3848(93)90119-9

Cited by 9 publications

(2 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Suzuki et al have found that proteose peptone is a potent inducer for t-PA production by IMR-90 cells and that the induction is closely related to the activation of phospholipase A2 and arachidonate metabolite(s) from lipoxygenase pathway (25)(26)(27). We have previously reported that thrombin increased t-PA mRNA levels in IMR-90 cells (28). In this paper, we report that thrombin increases the m RN A levels o f both l-PA and u-PA by enhancing the rales o f (heir gene transcriptions in IM R -90 eells.…”

Section: Introductionmentioning

confidence: 68%

See 1 more Smart Citation

Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes by Thrombin in Human Fetal Lung Fibroblasts

et al. 1995

Self Cite

View full text Add to dashboard Cite

SummaryThe mechanism of thrombin induction of tissue- and urokinase-type plasminogen activator (t-PA and u-PA) biosynthesis was investigated in cultured human fetal lung fibroblast cells, IMR-90. Northern blot analysis of total RNA from thrombin-treated cells showed marked accumulations of both t-PA and u-PA mRNA during 24 h. Nuclear run-on experiments showed that the transcription rates of both genes were increased in the thrombin-treated cells.These thrombin effects were inhibited by cycloheximide (CHX), an inhibitor of protein biosynthesis. Treatment of IMR-90 cells with CHX alone caused an increase in u-PA mRNA but not in t-PA mRNA. CHX, however, did not affect the transcription rates of both genes in the cells. Thus, on-going protein synthesis is required for increased accumulations of both t-PA and u-PA mRNA by thrombin but not for the constitutive expression of u-PA gene in IMR-90 cells. Therefore, we conclude that the accumulations of t-PA and u-PA mRNA due to thrombin result mainly from increased rates of their gene transcriptions, and that this influence is exerted in part by proteins synthesized by thrombin stimulation.Thrombin also increased plasminogen activator inhibitor type-1 (PAI-1) in the levels of both antigen and mRNA more rapidly than it increased t-PA in IMR-90 cells. In conditioned medium, most of the secreted PAI-1 seemed to form a complex with t-PA. Northern blot analysis using a PAI-2 cDNA probe showed that the levels of PAI-2 mRNA were markedly increased in response to thrombin. PAI-2 appeared not to have been secreted by the cells because the antigen was rarely detectable in the conditioned medium. Thus, thrombin increases not only plasminogen activators, but their inhibitors as well.

show abstract

Section: Introductionmentioning

confidence: 68%

“…Antigen determinations. For the measurement of antigens, IMR-90 cells were cultured in 24-well tissue culture plates (Coslar, Cambridge, MA, USA) as previously described (28). Conditioned medium was centrifuged to remove cellular debris and stored in aliquots at -30° C until further use.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes by Thrombin in Human Fetal Lung Fibroblasts

et al. 1995

Self Cite

View full text Add to dashboard Cite

show abstract

Effects of cadmium on the release of tissue plasminogen activator and plasminogen activator inhibitor type 1 from cultured human vascular smooth muscle cells and fibroblasts

et al. 1996

View full text Add to dashboard Cite

Coagulation and coagulation signalling in fibrosis

Mercer

Chambers

2013

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Following tissue injury, a complex and coordinated wound healing response comprising coagulation, inflammation, fibroproliferation and tissue remodelling has evolved to nullify the impact of the original insult and reinstate the normal physiological function of the affected organ. Tissue fibrosis is thought to result from a dysregulated wound healing response as a result of continual local injury or impaired control mechanisms. Although the initial insult is highly variable for different organs, in most cases, uncontrolled or sustained activation of mesenchymal cells into highly synthetic myofibroblasts leads to the excessive deposition of extracellular matrix proteins and eventually loss of tissue function. Coagulation was originally thought to be an acute and transient response to tissue injury, responsible primarily for promoting haemostasis by initiating the formation of fibrin plugs to enmesh activated platelets within the walls of damaged blood vessels. However, the last 20years has seen a major re-evaluation of the role of the coagulation cascade following tissue injury and there is now mounting evidence that coagulation plays a critical role in orchestrating subsequent inflammatory and fibroproliferative responses during normal wound healing, as well as in a range of pathological contexts across all major organ systems. This review summarises our current understanding of the role of coagulation and coagulation initiated signalling in the response to tissue injury, as well as the contribution of uncontrolled coagulation to fibrosis of the lung, liver, kidney and heart. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.

show abstract

Thrombin regulation of tissue-type plasminogen activator synthesis in cultured human fetal lung fibroblasts

Cited by 9 publications

References 32 publications

Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes by Thrombin in Human Fetal Lung Fibroblasts

Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes by Thrombin in Human Fetal Lung Fibroblasts

Effects of cadmium on the release of tissue plasminogen activator and plasminogen activator inhibitor type 1 from cultured human vascular smooth muscle cells and fibroblasts

Coagulation and coagulation signalling in fibrosis

Contact Info

Product

Resources

About