Tissue plasminogen activator mRNA in murine tissues

Rickles, Richard J.; Strickland, Sidney

doi:10.1016/0014-5793(88)80806-8

Cited by 45 publications

(17 citation statements)

References 38 publications

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“…1 B) was similar to that determined previously using ribonuclease protection assays (26) or Northern blotting approaches (13,47,48). For example, PAI-1 and t-PA mRNAs were detected in all tissues examined, although their concentrations varied over a wide range, and the expression of u-PA was more restricted than that of the other genes, with the highest concentration by far being in the kidney.…”

Section: Discussionsupporting

confidence: 86%

Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator.

Yamamoto

Loskutoff²

1996

J. Clin. Invest.

200

166

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The primary hypothesis of this report is that the formation and subsequent removal of fibrin in specific tissues during pathologic processes reflects temporal changes in the local expression of key procoagulant and fibrinolytic genes. To begin to test this hypothesis, we have used quantitative PCR assays and in situ hybridization analysis to examine the effects of endotoxin on the expression of specific genes in murine tissues, and to relate these changes to fibrin deposition/ dissolution using immunohistochemical approaches. Endotoxin caused large increases in plasminogen activator inhibitor-1 mRNA and modest increases in tissue factor mRNA in most tissues examined. However, fibrin was only detected in the kidneys and adrenals of endotoxin-treated mice, and it was transient. Unexpectedly, changes in urokinase-type plasminogen activator mRNA but not tissue-type plasminogen activator mRNA correlated with fibrin deposition/dissolution in these tissues. Pretreatment of mice with the fibrinolytic inhibitor epsilon-aminocaproic acid before endotoxin increased both the number of fibrin-positive tissues and the duration of fibrin deposition in the kidneys and adrenals. These results suggest that the absence of fibrin in some tissues reflects ongoing local fibrinolysis, and that increases in plasminogen activator inhibitor-1 and tissue factor gene expression and decreases in urokinase-type plasminogen activator expression are necessary for tissue-specific fibrin deposition. Changes in tissue-type plasminogen activator gene expression do not appear to be essential for fibrin deposition/dissolution in this murine model of sepsis. ( J. Clin. Invest. 1996. 97:2440-2451.)

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Section: Discussionsupporting

confidence: 86%

Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator.

Yamamoto

Loskutoff²

1996

J. Clin. Invest.

200

166

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“…2, A and B, lane 1, and Fig. 3, A and B) (37). The specificity of in situ hybridizations with these probes has already been established for other murine tissues (7,35); furthermore, in the kidney, the specificity of in situ hybridizations is supported by the nonoverlapping distribution of the signals detected by two probes from related genes.…”

Section: Resultsmentioning

confidence: 60%

Sites of synthesis of urokinase and tissue-type plasminogen activators in the murine kidney.

Sappino

Huarte²,

Vassalli³

et al. 1991

J. Clin. Invest.

153

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Kidneys have long been recognized as a major source of plasminogen activators (PAs). However, neither the sites of synthesis of the enzymes nor their role in renal function have been elucidated. By the combined use of zymographies on tissue sections and in situ hybridizations, we have explored the cellular distribution of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators and of their mRNAs in developing and adult mouse kidneys. In 17.5-d old embryos, renal tubules synthesize u-PA, while S-shaped bodies produce t-PA. In the adult kidney, u-PA is synthesized and released in urine by the epithelial cells lining the straight parts of both proximal and distal tubules. In contrast, t-PA is produced by glomerular cells and by epithelial cells lining the distal part of collecting ducts. The precise segmental distribution of PAs suggests that both enzymes may be implicated in the maintenance of tubular patency, by catalyzing extracellular proteolysis to prevent or circumvent protein precipitation. (J. Clin. Invest. 1991. 87:962-970.)

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“…As expected, Sl-resistant bands were not observed for samples that contained no detectable t-PA transcripts, such as tRNA, F9 stem cell RNA, or mouse liver RNA. However, for tissues that expressed the t-PA gene (53), a pattern of protected fragments whose sizes were the same as those obtained with F9-RA/cAMP RNA was generated. Thus, the same start sites of t-PA gene transcription are used by differentiated F9 cells and by t-PA-producing cells of the mouse.…”

Section: Resultsmentioning

confidence: 99%

Differentiation-responsive elements in the 5' region of the mouse tissue plasminogen activator gene confer two-stage regulation by retinoic acid and cyclic AMP in teratocarcinoma cells.

Rickles¹,

Darrow²,

Strickland³

1989

Mol. Cell. Biol.

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F9 cells induced to differentiate with retinoic acid (RA) increase transcription of the tissue plasminogen activator (t-PA) gene. Further treatment of these cells with cyclic AMP (cAMP) results in an additional stimulation of t-PA gene transcription. To investigate the mechanism of this two-stage regulation, 4 kilobase pairs (kbp) of 5'-flanking sequence from the murine t-PA gene was isolated. Two major start sites for transcription were found, neither of which depended on a classical TATA motif for correct initiation. By using transient transfection assays, it was determined that 4-kbp of flanking sequence could confer on reporter genes the same two-stage differentiation-specific expression as was observed for the endogenous t-PA gene. Deletion analyses of this 4-kbp fragment showed that 190 bp of flanking sequence was sufficient to bestow the same degree of two-stage regulation on reporter gene constructs. Within this region of DNA, sequence analysis revealed a possible cAMP regulatory element, a CTF/NF-1 recognition sequence, two potential Spl sites, and five potential binding sites for transcription factor AP-2. The deletion experiments, coupled with the positions of these potential cis-acting elements, suggest that multiple transcription factors, including those that bind to cAMP regulatory element, CTF/NF-1, Spl, and AP-2 sites, may be involved in regulation of the t-PA gene during F9 cell differentiation.

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Tissue plasminogen activator mRNA in murine tissues

Cited by 45 publications

References 38 publications

Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator.

Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator.

Sites of synthesis of urokinase and tissue-type plasminogen activators in the murine kidney.

Differentiation-responsive elements in the 5' region of the mouse tissue plasminogen activator gene confer two-stage regulation by retinoic acid and cyclic AMP in teratocarcinoma cells.

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