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Transcriptional regulation of tissue- and urokinase-type plasminogen activator genes by thrombin in human fetal lung fibroblasts.
Thromb Haemost 1995; 74(2):704-10TH

Abstract

The 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.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8585010

Citation

Hayakawa, Y, et al. "Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes By Thrombin in Human Fetal Lung Fibroblasts." Thrombosis and Haemostasis, vol. 74, no. 2, 1995, pp. 704-10.
Hayakawa Y, Tazawa S, Ishikawa T, et al. Transcriptional regulation of tissue- and urokinase-type plasminogen activator genes by thrombin in human fetal lung fibroblasts. Thromb Haemost. 1995;74(2):704-10.
Hayakawa, Y., Tazawa, S., Ishikawa, T., Niiya, K., & Sakuragawa, N. (1995). Transcriptional regulation of tissue- and urokinase-type plasminogen activator genes by thrombin in human fetal lung fibroblasts. Thrombosis and Haemostasis, 74(2), pp. 704-10.
Hayakawa Y, et al. Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes By Thrombin in Human Fetal Lung Fibroblasts. Thromb Haemost. 1995;74(2):704-10. PubMed PMID: 8585010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transcriptional regulation of tissue- and urokinase-type plasminogen activator genes by thrombin in human fetal lung fibroblasts. AU - Hayakawa,Y, AU - Tazawa,S, AU - Ishikawa,T, AU - Niiya,K, AU - Sakuragawa,N, PY - 1995/8/1/pubmed PY - 1995/8/1/medline PY - 1995/8/1/entrez SP - 704 EP - 10 JF - Thrombosis and haemostasis JO - Thromb. Haemost. VL - 74 IS - 2 N2 - The 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.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0340-6245 UR - https://www.unboundmedicine.com/medline/citation/8585010/Transcriptional_regulation_of_tissue__and_urokinase_type_plasminogen_activator_genes_by_thrombin_in_human_fetal_lung_fibroblasts_ DB - PRIME DP - Unbound Medicine ER -