Gene Symbol: tPA
Description: plasminogen activator, tissue
Alias: AU020998, AW212668, D8Ertd2e, tPA, tissue-type plasminogen activator, t-plasminogen activator
Species: mouse
Products:     tPA

Top Publications

  1. Tsirka S. Tissue plasminogen activator as a modulator of neuronal survival and function. Biochem Soc Trans. 2002;30:222-5 pubmed
    The tissue plasminogen activator (tPA)/plasmin proteolytic system has been implicated in both physiological and pathological processes in the mammalian brain. The physiological roles include facilitating neurite outgrowth and pathfinding...
  2. Fernandez Monreal M, Lopez Atalaya J, Benchenane K, Cacquevel M, Dulin F, Le Caer J, et al. Arginine 260 of the amino-terminal domain of NR1 subunit is critical for tissue-type plasminogen activator-mediated enhancement of N-methyl-D-aspartate receptor signaling. J Biol Chem. 2004;279:50850-6 pubmed
    Tissue-type plasminogen activator (tPA) has been involved in both physiological and pathological glutamatergic-dependent processes, such as synaptic plasticity, seizure, trauma, and stroke...
  3. Lund L, Green K, Stoop A, Ploug M, Almholt K, Lilla J, et al. Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice. EMBO J. 2006;25:2686-97 pubmed
    Simultaneous ablation of the two known activators of plasminogen (Plg), urokinase-type (uPA) and the tissue-type (tPA), results in a substantial delay in skin wound healing...
  4. Zhang X, Polavarapu R, She H, Mao Z, Yepes M. Tissue-type plasminogen activator and the low-density lipoprotein receptor-related protein mediate cerebral ischemia-induced nuclear factor-kappaB pathway activation. Am J Pathol. 2007;171:1281-90 pubmed
    Tissue-type plasminogen activator (tPA) is a serine proteinase found in the intravascular space and the central nervous system...
  5. Minor K, Phillips J, Seeds N. Tissue plasminogen activator promotes axonal outgrowth on CNS myelin after conditioned injury. J Neurochem. 2009;109:706-15 pubmed publisher
    ..The following study suggests that the proteolytic enzyme tissue plasminogen activator (tPA) plays a major function in 'conditioning-injury induced' axon regeneration...
  6. Lu W, Bhasin M, Tsirka S. Involvement of tissue plasminogen activator in onset and effector phases of experimental allergic encephalomyelitis. J Neurosci. 2002;22:10781-9 pubmed
    ..In the brains of MS patients, tissue plasminogen activator (tPA) mRNA and protein are upregulated, and changes in the levels of tPA correlate with progression of the disease...
  7. Yamamoto K, Loskutoff D. Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator. J Clin Invest. 1996;97:2440-51 pubmed
    ..Changes in tissue-type plasminogen activator gene expression do not appear to be essential for fibrin deposition/dissolution in this murine model of sepsis. ..
  8. An J, Zhang C, Polavarapu R, Zhang X, Zhang X, Yepes M. Tissue-type plasminogen activator and the low-density lipoprotein receptor-related protein induce Akt phosphorylation in the ischemic brain. Blood. 2008;112:2787-94 pubmed publisher
    Tissue-type plasminogen activator (tPA) is found in the intravascular space and in the central nervous system. The low-density lipoprotein receptor-related protein (LRP) is expressed in neurons and in perivascular astrocytes...
  9. Chen Z, Indyk J, Bugge T, Kombrinck K, Degen J, Strickland S. Neuronal death and blood-brain barrier breakdown after excitotoxic injury are independent processes. J Neurosci. 1999;19:9813-20 pubmed
    ..These results indicate that excitotoxin-induced neuronal death and BBB breakdown are separable events in the hippocampus. ..

More Information


  1. Samson A, Medcalf R. Tissue-type plasminogen activator: a multifaceted modulator of neurotransmission and synaptic plasticity. Neuron. 2006;50:673-8 pubmed
  2. Guo Y, Li J, Hagström E, Ny T. Beneficial and detrimental effects of plasmin(ogen) during infection and sepsis in mice. PLoS ONE. 2011;6:e24774 pubmed publisher
    ..In this study, by using mice lacking genes for plasminogen, tissue-type plasminogen activator (tPA), and urokinase-type PA (uPA), we have investigated the functional roles of active plasmin in infection and sepsis...
  3. Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen J, Bronson R, et al. Physiological consequences of loss of plasminogen activator gene function in mice. Nature. 1994;368:419-24 pubmed
    ..Mice with combined t-PA and u-PA deficiency suffer extensive spontaneous fibrin deposition, with its associated effects on growth, fertility and survival. ..
  4. Siconolfi L, Seeds N. Mice lacking tPA, uPA, or plasminogen genes showed delayed functional recovery after sciatic nerve crush. J Neurosci. 2001;21:4348-55 pubmed
    ..These proteases include the plasminogen activators (PAs), tissue PA (tPA) and urokinase PA (uPA), and their substrate, plasminogen...
  5. Bugge T, Flick M, Danton M, Daugherty C, Romer J, Dano K, et al. Urokinase-type plasminogen activator is effective in fibrin clearance in the absence of its receptor or tissue-type plasminogen activator. Proc Natl Acad Sci U S A. 1996;93:5899-904 pubmed the urokinase-type plasminogen activator (uPA), urokinase receptor (uPAR), tissue-type plasminogen activator (tPA), and plasminogen permits a critical, genetic-based analysis of the physiological and pathological roles of the two ..
  6. Jögi A, Rønø B, Lund I, Nielsen B, Ploug M, Høyer Hansen G, et al. Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice. PLoS ONE. 2010;5:e12746 pubmed publisher
    ..the two plasminogen activators, urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA)...
  7. Fredriksson L, Li H, Fieber C, Li X, Eriksson U. Tissue plasminogen activator is a potent activator of PDGF-CC. EMBO J. 2004;23:3793-802 pubmed
    Tissue plasminogen activator (tPA) is a serine protease involved in the degradation of blood clots through the activation of plasminogen to plasmin...
  8. Frey U, Muller M, Kuhl D. A different form of long-lasting potentiation revealed in tissue plasminogen activator mutant mice. J Neurosci. 1996;16:2057-63 pubmed
    ..Most remarkably, t-PA-deficient mice exhibit a different form of long-lasting potentiation that is characterized by an NMDA receptor-dependent modification of GABA transmission in the CA1 region. ..
  9. Devy L, Blacher S, Grignet Debrus C, Bajou K, Masson V, Gerard R, et al. The pro- or antiangiogenic effect of plasminogen activator inhibitor 1 is dose dependent. FASEB J. 2002;16:147-54 pubmed
    ..The single deficiency of tPA, uPA, or uPAR, as well as combined deficiencies of uPA and tPA, did not dramatically affect microvessel formation...
  10. Pang P, Teng H, Zaitsev E, Woo N, Sakata K, Zhen S, et al. Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science. 2004;306:487-91 pubmed
    ..Two secretory proteins, tissue plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF), have been implicated in this process, but their relationship is ..
  11. Kawasaki T, Dewerchin M, Lijnen H, Vreys I, Vermylen J, Hoylaerts M. Mouse carotid artery ligation induces platelet-leukocyte-dependent luminal fibrin, required for neointima development. Circ Res. 2001;88:159-66 pubmed
    ..Delayed coagulation then results in formation of a fibrin matrix, which is used by smooth muscle cells to migrate into the lumen. ..
  12. Nagai N, De Mol M, Lijnen H, Carmeliet P, Collen D. Role of plasminogen system components in focal cerebral ischemic infarction: a gene targeting and gene transfer study in mice. Circulation. 1999;99:2440-4 pubmed
    ..FCI) was studied in mice deficient in plasminogen (Plg-/-), in tissue or urokinase plasminogen activator (tPA-/- or uPA-/-), or in plasminogen activator inhibitor-1 or alpha2-antiplasmin (PAI-1(-/-) or alpha2-AP-/-)...
  13. Park L, Gallo E, Anrather J, Wang G, Norris E, Paul J, et al. Key role of tissue plasminogen activator in neurovascular coupling. Proc Natl Acad Sci U S A. 2008;105:1073-8 pubmed publisher
    ..Here, we show that tissue plasminogen activator (tPA), a serine protease implicated in NMDA receptor signaling, is required for the flow increase evoked by ..
  14. Tsirka S, Rogove A, Bugge T, Degen J, Strickland S. An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J Neurosci. 1997;17:543-52 pubmed
    Mice lacking the serine protease tissue plasminogen activator (tPA) are resistant to excitotoxin-mediated hippocampal neuronal degeneration. We have used genetic and cellular analyses to study the role of tPA in neuronal cell death...
  15. Nolin W, Emmetsberger J, Bukhari N, Zhang Y, Levine J, Tsirka S. tPA-mediated generation of plasmin is catalyzed by the proteoglycan NG2. Glia. 2008;56:177-89 pubmed
    ..we describe here a potentially synergistic therapeutic opportunity based on tissue plasminogen activator (tPA), an extracellular protease that converts plasminogen (plg) into the active protease plasmin...
  16. Lee S, Lok J, Rosell A, Kim H, Murata Y, Atochin D, et al. Reduction of hippocampal cell death and proteolytic responses in tissue plasminogen activator knockout mice after transient global cerebral ischemia. Neuroscience. 2007;150:50-7 pubmed
    Knockout mice deficient in tissue plasminogen activator (tPA) are protected against hippocampal excitotoxicity...
  17. Tsirka S, Gualandris A, Amaral D, Strickland S. Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature. 1995;377:340-4 pubmed
    ..When neuronal activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to the active protease plasmin, is transcriptionally induced...
  18. Chen Z, Indyk J, Strickland S. The hippocampal laminin matrix is dynamic and critical for neuronal survival. Mol Biol Cell. 2003;14:2665-76 pubmed
    ..2) was posttranscriptional, because there was no effect on laminin mRNA expression; and 3) occurred in both tPA(-/-) and plasminogen(-/-) mice, indicating that increased plasmin activity was not responsible...
  19. Benchenane K, Berezowski V, Ali C, Fernandez Monreal M, Lopez Atalaya J, Brillault J, et al. Tissue-type plasminogen activator crosses the intact blood-brain barrier by low-density lipoprotein receptor-related protein-mediated transcytosis. Circulation. 2005;111:2241-9 pubmed
    Accumulating evidence demonstrates a critical involvement of tissue-type plasminogen activator (tPA) in pathological and physiological brain conditions...
  20. Lu W, Tsirka S. Partial rescue of neural apoptosis in the Lurcher mutant mouse through elimination of tissue plasminogen activator. Development. 2002;129:2043-50 pubmed
    ..stroke) is promoted by an extracellular cascade involving the serine protease tissue plasminogen activator (tPA)...
  21. Chen Z, Strickland S. Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin. Cell. 1997;91:917-25 pubmed
    ..acids can provoke neuronal death in the hippocampus, and the extracellular proteases tissue plasminogen activator (tPA) and plasmin (ogen) have been implicated in this death...
  22. Melchor J, Pawlak R, Strickland S. The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-beta (Abeta) degradation and inhibits Abeta-induced neurodegeneration. J Neurosci. 2003;23:8867-71 pubmed
    ..To better define clearance pathways, we have evaluated the role of the tissue plasminogen activator (tPA)-plasmin system in Abeta degradation in vivo...
  23. Wang H, Zhang Y, Heuckeroth R. Tissue-type plasminogen activator deficiency exacerbates cholestatic liver injury in mice. Hepatology. 2007;45:1527-37 pubmed
    ..activator inhibitor (PAI)-1 in cholestatic liver disease in mice suggested that tissue-type plasminogen activator (tPA) or urokinase plasminogen activator (uPA) might be important after biliary tract obstruction...
  24. Roussel B, Hommet Y, Macrez R, Schulz T, Petersen K, Berezowski V, et al. PPACK-Desmodus rotundus salivary plasminogen activator (cDSPAalpha1) prevents the passage of tissue-type plasminogen activator (rt-PA) across the blood-brain barrier and neurotoxicity. Thromb Haemost. 2009;102:606-8 pubmed publisher
  25. Rao G, Alland L, Guida P, Schreiber Agus N, Chen K, Chin L, et al. Mouse Sin3A interacts with and can functionally substitute for the amino-terminal repression of the Myc antagonist Mxi1. Oncogene. 1996;12:1165-72 pubmed
  26. Piguet P, Vesin C, Da Laperousaz C, Rochat A. Role of plasminogen activators and urokinase receptor in platelet kinetics. Hematol J. 2000;1:199-205 pubmed
    ..We took advantage of genetically deficient mice to explore the role of urokinase (uPA) and tissue type (tPA) PAs, as well as the uPA receptor (uPAR, CD87) in platelet kinetics...
  27. Boyle A, Feltquite D, Dracopoli N, Housman D, Ward D. Rapid physical mapping of cloned DNA on banded mouse chromosomes by fluorescence in situ hybridization. Genomics. 1992;12:106-15 pubmed
    ..Clones hybridizing to each murine chromosome have been identified, thus providing a panel of marker probes to assist in chromosome identification. ..
  28. Oh S, Byun C, Yun J, Jo D, Carmeliet P, Koh J, et al. Tissue plasminogen activator arrests Alzheimer's disease pathogenesis. Neurobiol Aging. 2014;35:511-9 pubmed publisher
    ..This study was aimed to determine whether endogenous tissue plasminogen activator (tPA) modulates the pathogenic process of AD...
  29. Bahi A, Dreyer J. Involvement of tissue plasminogen activator "tPA" in ethanol-induced locomotor sensitization and conditioned-place preference. Behav Brain Res. 2012;226:250-8 pubmed publisher
    ..In our previous studies we have shown that the serine protease tissue plasminogen activator (tPA) is involved in the rewarding properties of morphine and amphetamine...
  30. Correa F, Gauberti M, Parcq J, Macrez R, Hommet Y, Obiang P, et al. Tissue plasminogen activator prevents white matter damage following stroke. J Exp Med. 2011;208:1229-42 pubmed publisher
    Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within the brain, ranging from synaptic plasticity to control of cell fate...
  31. Roelofs J, Rouschop K, Teske G, Wagenaar G, Claessen N, Weening J, et al. Endogenous tissue-type plasminogen activator is protective during ascending urinary tract infection. Nephrol Dial Transplant. 2009;24:801-8 pubmed publisher
    Acute pyelonephritis is one of the most common bacterial infections. Tissue-type plasminogen activator (tPA) is a potent fibrinolytic agent, but can play a role in inflammatory processes as well...
  32. Levin E, Santell L, Osborn K. The expression of endothelial tissue plasminogen activator in vivo: a function defined by vessel size and anatomic location. J Cell Sci. 1997;110 ( Pt 2):139-48 pubmed
    Plasma tissue plasminogen activator (tPA) has long been considered to be the product of the endothelial cells that line the various parts of the vascular system regardless of vessel size or location...
  33. Wang H, Zhang Y, Heuckeroth R. PAI-1 deficiency reduces liver fibrosis after bile duct ligation in mice through activation of tPA. FEBS Lett. 2007;581:3098-104 pubmed
    ..This change correlated with increased tissue-type plasminogen activator (tPA) activity, and increased matrix metalloproteinase-9 (MMP-9), but not MMP-2 activity...
  34. Parathath S, Parathath S, Tsirka S. Nitric oxide mediates neurodegeneration and breakdown of the blood-brain barrier in tPA-dependent excitotoxic injury in mice. J Cell Sci. 2006;119:339-49 pubmed
    ..a complex signaling pathway that includes the participation of the serine protease tissue plasminogen activator (tPA)...
  35. Krstic D, Rodríguez M, Knuesel I. Regulated proteolytic processing of Reelin through interplay of tissue plasminogen activator (tPA), ADAMTS-4, ADAMTS-5, and their modulators. PLoS ONE. 2012;7:e47793 pubmed publisher
    ..Here we identified the serine protease tissue plasminogen activator (tPA) and two matrix metalloproteinases, ADAMTS-4 and ADAMTS-5, as Reelin cleaving enzymes...
  36. Labeyrie P, Goulay R, Martinez de Lizarrondo S, Hébert M, Gauberti M, Maubert E, et al. Vascular Tissue-Type Plasminogen Activator Promotes Intracranial Aneurysm Formation. Stroke. 2017;48:2574-2582 pubmed publisher
    ..Because tPA (tissue-type plasminogen activator) controls both inflammatory and matrix remodeling processes, we hypothesized ..
  37. Everts V, Daci E, Tigchelaar Gutter W, Hoeben K, Torrekens S, Carmeliet G, et al. Plasminogen activators are involved in the degradation of bone by osteoclasts. Bone. 2008;43:915-20 pubmed publisher
    ..Yet, several findings suggest that the two types of plasminogen activators (PA), the tissue- and urokinase-type PA (tPA and uPA, respectively) are also involved in this process...
  38. Jensen P, Lavker R. Modulation of the plasminogen activator cascade during enhanced epidermal proliferation in vivo. Cell Growth Differ. 1996;7:1793-804 pubmed
  39. Ceci J, Justice M, Lock L, Jenkins N, Copeland N. An interspecific backcross linkage map of mouse chromosome 8. Genomics. 1990;6:72-9 pubmed
    ..A conserved linkage group was identified between mouse chromosome 8 and human chromosome 16. The map will be useful for establishing linkage of other markers to mouse chromosome 8. ..
  40. Yepes M, Sandkvist M, Moore E, Bugge T, Strickland D, Lawrence D. Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J Clin Invest. 2003;112:1533-40 pubmed
    ..In this study we demonstrate that an increase in endogenous tissue-type plasminogen activator (tPA) activity in the perivascular tissue following cerebral ischemia induces opening of the BBB via a mechanism that is ..
  41. Pawlak R, Magarinos A, Melchor J, McEwen B, Strickland S. Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior. Nat Neurosci. 2003;6:168-74 pubmed
    ..Here we found that the serine protease tissue-plasminogen activator (tPA) was upregulated in the central and medial amygdala by acute restraint stress, where it promoted stress-related ..
  42. Sato J, Schorey J, Ploplis V, Haalboom E, Krahule L, Castellino F. The fibrinolytic system in dissemination and matrix protein deposition during a mycobacterium infection. Am J Pathol. 2003;163:517-31 pubmed
    ..avium from lungs. Thus, plasmin(ogen) functions in limiting progressive fibrosis in the granuloma during a chronic mycobacterial infection. ..
  43. Pawlak R, Rao B, Melchor J, Chattarji S, McEwen B, Strickland S. Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc Natl Acad Sci U S A. 2005;102:18201-6 pubmed
    ..spatially with sites of plasminogen activation, thereby predicting a role for tissue plasminogen activator (tPA) in this form of stress-induced plasticity...
  44. Sorrell A, Shand J, Tonner E, Gamberoni M, Accorsi P, Beattie J, et al. Insulin-like growth factor-binding protein-5 activates plasminogen by interaction with tissue plasminogen activator, independently of its ability to bind to plasminogen activator inhibitor-1, insulin-like growth factor-I, or heparin. J Biol Chem. 2006;281:10883-9 pubmed
    ..In a cell-free system, using tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) to activate plasminogen, PAI-1 inhibited plasmin generation induced by ..
  45. Denorme F, Langhauser F, Desender L, Vandenbulcke A, Rottensteiner H, Plaimauer B, et al. ADAMTS13-mediated thrombolysis of t-PA-resistant occlusions in ischemic stroke in mice. Blood. 2016;127:2337-45 pubmed publisher
    ..05). These data show for the first time a potent thrombolytic activity of ADAMTS13 in the setting of stroke, which might become useful in treatment of acute ischemic stroke. ..
  46. Horii Hayashi N, Yoshikawa M, Matsusue Y, Ishizaka S, Nishi M, Wanaka A. Environmental stimulation changes tissue-type plasminogen activator activity in the adult mouse hippocampus. Neurochem Int. 2011;58:1-4 pubmed publisher
    Tissue-type plasminogen activator (tPA) plays an important role in synaptic plasticity and contributes to several brain functions such as memory, learning, and behaviours...
  47. Dhahri D, Sato Kusubata K, Ohki Koizumi M, Nishida C, Tashiro Y, Munakata S, et al. Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells. Blood. 2016;128:1063-75 pubmed publisher
    Tissue plasminogen activator (tPA), aside from its vascular fibrinolytic action, exerts various effects within the body, ranging from synaptic plasticity to control of cell fate...
  48. Kuo S, Mellentin J, Copeland N, Gilbert D, Jenkins N, Cleary M. Structure, chromosome mapping, and expression of the mouse Lyl-1 gene. Oncogene. 1991;6:961-8 pubmed
    ..We conclude that LYL1 has the properties of a lineage- and differentiation-specific HLH protein that contributes to T-cell neoplasia through its deregulated expression following chromosomal translocation. ..
  49. Hosler B, Rogers M, Kozak C, Gudas L. An octamer motif contributes to the expression of the retinoic acid-regulated zinc finger gene Rex-1 (Zfp-42) in F9 teratocarcinoma cells. Mol Cell Biol. 1993;13:2919-28 pubmed
  50. Sachs B, Baillie G, McCall J, Passino M, Schachtrup C, Wallace D, et al. p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway. J Cell Biol. 2007;177:1119-32 pubmed
    ..after tissue injury, blocks fibrinolysis by down-regulating the serine protease, tissue plasminogen activator (tPA), and up-regulating plasminogen activator inhibitor-1 (PAI-1)...
  51. Suzuki Y, Nagai N, Yamakawa K, Kawakami J, Lijnen H, Umemura K. Tissue-type plasminogen activator (t-PA) induces stromelysin-1 (MMP-3) in endothelial cells through activation of lipoprotein receptor-related protein. Blood. 2009;114:3352-8 pubmed publisher
    ..These findings indicate that t-PA deteriorates ICB via MMP-3 induction in endothelial cells, which is regulated through the LRP/nuclear factor-kappaB pathway. ..
  52. Nassar T, Yarovoi S, Fanne R, Akkawi S, Jammal M, Allen T, et al. Regulation of airway contractility by plasminogen activators through N-methyl-D-aspartate receptor-1. Am J Respir Cell Mol Biol. 2010;43:703-11 pubmed publisher
    ..Both tissue-type PA (tPA) and urokinase-type PA (uPA) bind to NMDA-R1 and reverse this effect, thereby enhancing Ach-induced tracheal ..
  53. Nagai T, Noda Y, Ishikawa K, Miyamoto Y, Yoshimura M, Ito M, et al. The role of tissue plasminogen activator in methamphetamine-related reward and sensitization. J Neurochem. 2005;92:660-7 pubmed
    In the central nervous system, tissue plasminogen activator (tPA) plays a role in synaptic plasticity and remodeling...
  54. Pineda D, Ampurdanés C, Medina M, Serratosa J, Tusell J, Saura J, et al. Tissue plasminogen activator induces microglial inflammation via a noncatalytic molecular mechanism involving activation of mitogen-activated protein kinases and Akt signaling pathways and AnnexinA2 and Galectin-1 receptors. Glia. 2012;60:526-40 pubmed publisher
    ..Tissue plasminogen activator (tPA) is a serine protease which best-known function is fibrinolysis, but it is also involved in many other ..
  55. Seeds N, Basham M, Haffke S. Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene. Proc Natl Acad Sci U S A. 1999;96:14118-23 pubmed
    ..In the developing cerebellum, granule neurons turn on the gene for tissue plasminogen activator (tPA) as they begin their migration into the cerebellar molecular layer...
  56. Yamamoto K, Loskutoff D, Saito H. Renal expression of fibrinolytic genes and tissue factor in a murine model of renal disease as a function of age. Semin Thromb Hemost. 1998;24:261-8 pubmed
  57. Lee S, Ko H, Kwon K, Lee J, Han S, Han D, et al. tPA regulates neurite outgrowth by phosphorylation of LRP5/6 in neural progenitor cells. Mol Neurobiol. 2014;49:199-215 pubmed publisher
    Despite the important role of tissue plasminogen activator (tPA) as a neuromodulator in neurons, microglia, and astrocytes, its role in neural progenitor cell (NPC) development is not clear yet...
  58. Friedman G, Seeds N. Tissue plasminogen activator mRNA expression in granule neurons coincides with their migration in the developing cerebellum. J Comp Neurol. 1995;360:658-70 pubmed
    ..Thus, tissue plasminogen activator gene expression is induced as granule neurons leave the external granule layer and begin their inward migration. ..
  59. Madani R, Hulo S, Toni N, Madani H, Steimer T, Muller D, et al. Enhanced hippocampal long-term potentiation and learning by increased neuronal expression of tissue-type plasminogen activator in transgenic mice. EMBO J. 1999;18:3007-12 pubmed
    Adult cortical neurons can produce tissue-type plasminogen activator (tPA), an extracellular protease that plays a critical role in fibrinolysis and tissue remodelling processes...
  60. Irigoyen J, Munoz Canoves P, Montero L, Koziczak M, Nagamine Y. The plasminogen activator system: biology and regulation. Cell Mol Life Sci. 1999;56:104-32 pubmed
    ..Thus, modulation of mRNA stability is an important factor in overall regulation. This review summarizes current understanding of the biology and regulation of genes involved in plasminogen activation at different levels. ..
  61. Valenzuela D, Griffiths J, Rojas J, Aldrich T, Jones P, Zhou H, et al. Angiopoietins 3 and 4: diverging gene counterparts in mice and humans. Proc Natl Acad Sci U S A. 1999;96:1904-9 pubmed
    ..Angiopoietin-3 and angiopoietin-4 have very different distributions in their respective species, and angiopoietin-3 appears to act as an antagonist, whereas angiopoietin-4 appears to function as an agonist. ..
  62. Stutz A, Huarte J, Gubler P, Conne B, Belin D, Vassalli J. In vivo antisense oligodeoxynucleotide mapping reveals masked regulatory elements in an mRNA dormant in mouse oocytes. Mol Cell Biol. 1997;17:1759-67 pubmed
    In mouse oocytes, tissue-type plasminogen activator (tPA) mRNA is under translational control...
  63. Chen Z, Yu H, Yu W, Pawlak R, Strickland S. Proteolytic fragments of laminin promote excitotoxic neurodegeneration by up-regulation of the KA1 subunit of the kainate receptor. J Cell Biol. 2008;183:1299-1313 pubmed publisher
    ..KA1 levels in tissue plasminogen activator (tPA)-KO mice were also unchanged after KA, indicating that both tPA and laminin were necessary for KA1 up-regulation ..
  64. Ida A, Hirose S, Hamano Y, Kodera S, Jiang Y, Abe M, et al. Multigenic control of lupus-associated antiphospholipid syndrome in a model of (NZW x BXSB) F1 mice. Eur J Immunol. 1998;28:2694-703 pubmed
    ..e. BXSB Yaa and some from NZW, characterizes unique SLE features in male (NZW x BXSB) F1 mice. There are potentially important candidate genes which may be linked to the syndrome. ..
  65. Mecenas P, Tsirka S, Salles F, Strickland S. Removal of tissue plasminogen activator does not protect against neuronal degeneration in the cerebellum of the weaver mouse. Brain Res. 1997;772:233-8 pubmed
    Tissue plasminogen activator (tPA) is a serine protease that has been shown to be involved in neuronal degeneration. Recently, elevated cerebellar tPA has been reported in a naturally occurring mutant mouse, weaver...
  66. Marcos Contreras O, Martinez de Lizarrondo S, Bardou I, Orset C, Pruvost M, Anfray A, et al. Hyperfibrinolysis increases blood-brain barrier permeability by a plasmin- and bradykinin-dependent mechanism. Blood. 2016;128:2423-2434 pubmed
    ..state in mice by hydrodynamic transfection of a plasmid encoding for tissue-type plasminogen activator (tPA)...
  67. Weiler Guettler H, Christie P, Beeler D, Healy A, Hancock W, Rayburn H, et al. A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state. J Clin Invest. 1998;101:1983-91 pubmed
    ..The thrombomodulin-deficient animals provide a murine model to examine known or identify unknown genetic and environmental factors that lead to the development of thrombosis. ..
  68. Berta T, Liu Y, Xu Z, Ji R. Tissue plasminogen activator contributes to morphine tolerance and induces mechanical allodynia via astrocytic IL-1? and ERK signaling in the spinal cord of mice. Neuroscience. 2013;247:376-85 pubmed publisher
    ..Tissue plasminogen activator (tPA) is a serine protease that has been extensively used to treat stroke...
  69. Koizumi T, Hendel E, Lalley P, Tchetgen M, Nadeau J. Homologs of genes and anonymous loci on human chromosome 13 map to mouse chromosomes 8 and 14. Mamm Genome. 1995;6:263-8 pubmed
    ..Finally, we identified either a closely linked sequence related to Col4a2, or a recombination hot-spot between Col4a1 and Col4a2 that has been conserved in humans and mice. ..
  70. Leu S, Lu H, Sun C, Sheu J, Chen Y, Tsai T, et al. Retention of endothelial progenitor cells in bone marrow in a murine model of endogenous tissue plasminogen activator (tPA) deficiency in response to critical limb ischemia. Int J Cardiol. 2014;170:394-405 pubmed publisher
    This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating the left ..
  71. Hua H, Zhang R, Wang H, Zhao Y, Yu S, Li W. Tissue-type plasminogen activator depletion affects the nasal mucosa matrix reconstruction in allergic rhinitis mice. Allergol Immunopathol (Madr). 2011;39:206-11 pubmed publisher
    ..MMP-9 expression decreased greatly after ovalbumin challenge in t-PA(-/-) mice. t-PA affects the nasal mucosa matrix reconstruction process in allergic rhinitis, with which MMP-9 is involved. ..
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  73. Liu Y, Du Q, Hu Z, Tor N. Hormonal regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 gene expression in cultured mouse Sertoli cells. Sci China B. 1993;36:319-28 pubmed
    We have demonstrated for the first time that (i) mouse Sertoli cells predominantly secrete tPA under the action of FSH and cAMP-generating agents, whereas Leydig cells mainly produce uPA; (ii) Sertoli cells are also capable of secreting ..
  74. Hennebert O, Laudenbach V, Laquerriere A, Verney C, Carmeliet P, Marret S, et al. Ontogenic study of the influence of tissue plasminogen activator (t-PA) in neonatal excitotoxic brain insult and the subsequent microglia/macrophage activation. Neuroscience. 2005;130:697-712 pubmed
    ..Conversely, t-PA was implicated in cyst formation in older (P2-P10) mice, and in their subsequent growth. t-PA was also involved in GM lesions, probably through an inflammatory process involving macrophages. ..
  75. Yang Y, Carmeliet P, Hamilton J. Tissue-type plasminogen activator deficiency exacerbates arthritis. J Immunol. 2001;167:1047-52 pubmed
    ..Fibrin deposition appeared to parallel disease severity under the various conditions, suggesting that PA-mediated fibrinolysis may be normally playing a protective role in inflammatory joint disease. ..
  76. Carmeliet P, Collen D. Genetic analysis of the plasminogen and coagulation system in mice. Haemostasis. 1996;26 Suppl 4:132-53 pubmed
  77. Hovius J, Bijlsma M, van der Windt G, Wiersinga W, Boukens B, Coumou J, et al. The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. PLoS Pathog. 2009;5:e1000447 pubmed publisher
    ..B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity) and PAI-1 (high fibrinolytic activity) knock-out mice compared to WT controls...
  78. Gu R, Fu L, Jiang C, Xu Y, Wang X, Yu J. Retina Is Protected by Neuroserpin from Ischemic/Reperfusion-Induced Injury Independent of Tissue-Type Plasminogen Activator. PLoS ONE. 2015;10:e0130440 pubmed publisher
    ..An IR injury model was established by elevating intraocular pressure (IOP) for 60 minutes in wild type and tPA-deficient (tPA-/-) mice...
  79. Louessard M, Lacroix A, Martineau M, Mondielli G, Montagne A, Lesept F, et al. Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons. Mol Neurobiol. 2016;53:5000-12 pubmed publisher
    Although the extracellular serine protease tissue plasminogen activator (tPA) is involved in pathophysiological processes such as learning and memory, anxiety, epilepsy, stroke, and Alzheimer's disease, information about its regional, ..
  80. Ito M, Nagai T, Mizoguchi H, Fukakusa A, Nakanishi Y, Kamei H, et al. Possible involvement of protease-activated receptor-1 in the regulation of morphine-induced dopamine release and hyperlocomotion by the tissue plasminogen activator-plasmin system. J Neurochem. 2007;101:1392-9 pubmed
    We have previously demonstrated that tissue plasminogen activator (tPA)-plasmin system participates in the rewarding effect of morphine, by regulating dopamine release in the nucleus accumbens (NAc)...
  81. Baron A, Hommet Y, Cassé F, Vivien D. Tissue-type plasminogen activator induces plasmin-dependent proteolysis of intracellular neuronal nitric oxide synthase. Biol Cell. 2010;102:539-47 pubmed publisher
    Despite its pro-fibrinolytic activity, tPA (tissue plasminogen activator) is a serine protease known to influence a number of physiological and pathological functions in the central nervous system...
  82. Thewke D, Seeds N. Expression of hepatocyte growth factor/scatter factor, its receptor, c-met, and tissue-type plasminogen activator during development of the murine olfactory system. J Neurosci. 1996;16:6933-44 pubmed
    ..system and compared with the expression of a known activator of HGF/SF, tissue-type plasminogen activator (tPA)...
  83. Shushakova N, Eden G, Dangers M, Zwirner J, Menne J, Gueler F, et al. The urokinase/urokinase receptor system mediates the IgG immune complex-induced inflammation in lung. J Immunol. 2005;175:4060-8 pubmed
    ..The findings indicate an important link between the uPA/uPAR system and the two main components involved in the IC inflammation, namely, complement and FcgammaRs...