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Gene Review

Plg  -  plasminogen

Mus musculus

Synonyms: AI649309, Pg, Plasminogen
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Disease relevance of Plg

  • However, Plg-/- mice are predisposed to severe thrombosis, and young animals developed multiple spontaneous thrombotic lesions in liver, stomach, colon, rectum, lung, pancreas, and other tissues [1].
  • In contrast, proMMP-9 or actMMP-9, but not Plg, reconstituted susceptibility of MMP-9-deficient mice to the skin disease [2].
  • We demonstrate that a Plg cascade synergizes with MMP-9/gelatinase B in vivo during dermal-epidermal separation in an experimental model of bullous pemphigoid (BP), an autoimmune disease [2].
  • Conclusions: Plg/plasmin deficiency leads to features similar to those found in chronic pancreatitis such as parenchymal atrophy and fibrosis [3].
  • Histological examination of several organs revealed fibrin deposition in the liver; lung; and in the stomach, associated with gastric ulcers, in 6- to 12-week-old Plg-/- mice but not in Plg+/+ or Plg+/- littermates [4].

Psychiatry related information on Plg


High impact information on Plg

  • Successive passages (more than three) of cultures established from the tumors resulted in complete depletion of macrophages; steady-state MME mRNA, elastinolytic activity, and production of angiostatin (in the presence of plasminogen) were correspondingly reduced [6].
  • The role of the host plasminogen activation system in transmission of and invasion by Borrelia burgdorferi, the tick-borne spirochetal agent of Lyme disease, was investigated using plasminogen (Plg)-knockout mice [7].
  • These data suggest that the fundamental and possibly only essential physiological role of Plg is fibrinolysis [8].
  • Plasminogen (Plg) deficiency in mice results in high mortality, wasting, spontaneous gastrointestinal ulceration, rectal prolapse, and severe thrombosis [8].
  • Furthermore, Plg-deficient mice display delayed wound healing following skin injury, a defect partly related to impaired keratinocyte migration [8].

Chemical compound and disease context of Plg


Biological context of Plg


Anatomical context of Plg


Associations of Plg with chemical compounds

  • In vivo administration of a plasma kallikrein (pKal)-selective form of the serine protease inhibitor ecotin exacerbates the healing impairment of uPA;tPA double-deficient wounds to a degree indistinguishable from that observed in Plg-deficient mice, and completely blocks the activity of pKal, but not uPA and tPA in wound extracts [18].
  • Skin wounds in uPA;tPA-deficient mice treated with the broad-spectrum matrix metalloproteinase (MMP) inhibitor galardin (N-[(2R)-2-(hydroxamido-carbonylmethyl)-4-methylpentanoyl]-L-tryptophan methylamide) eventually heal, whereas skin wounds in galardin-treated Plg-deficient mice do not heal [18].
  • Strikingly, the stress-induced decrease in NMDA receptors coincides spatially with sites of plasminogen activation, thereby predicting a role for tissue plasminogen activator (tPA) in this form of stress-induced plasticity [19].
  • Plasminogen Activator Inhibitor Type-1-Deficient Mice Have an Enhanced IFN-{gamma} Response to Lipopolysaccharide and Staphylococcal Enterotoxin B [20].
  • Analysis of microsomes by zymography demonstrated a single band of proteolytic activity at 70-kDa corresponding to the mobility of Pg in nonreduced polyacrylamide gels [21].
  • The reduced serum progesterone levels in plg-deficient mice suggest that plasmin, but not MMPs, plays a role in maintenance of luteal function [22].

Physical interactions of Plg

  • Furthermore, these two traits appeared to be regulated by a complementary effect of two BXSB alleles; one is linked to Plat and the other to the H-2 complex and the gene for plasminogen [23].
  • This activation was associated with decreased levels of mRNA encoding latent TGF-beta-binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44 [24].
  • These results suggest that uPA binding to integrins through the kringle domain plays an important role in both plasminogen activation and uPA-induced intracellular signaling [25].
  • The clone with the highest PAI-2 expression exhibited complete inhibition of soluble and cell-surface-bound plasminogen activator activity [26].
  • Although neuroserpin bound and inactivated plasminogen activators and plasmin, no interaction was observed with thrombin [27].

Enzymatic interactions of Plg


Regulatory relationships of Plg

  • Injection of plasminogen induced a variable increase (on average 7- to 10-fold) of PAI-1, but no correlation with the extent of spontaneous clot lysis was observed [30].
  • Here, we define the molecular mechanisms of liver injury and explore whether uPA can regulate liver repair independently of plasminogen [31].
  • Furthermore, Plg stimulated DNA binding activity of the transcription factors activator-protein 1 and early growth response gene-1 to their cognate regulatory sequences at alpha-ENO promoter [32].
  • Furthermore, plasminogen stimulated CREB and NF-kappaB DNA binding activity, and this activation was also reduced by trolox and NAC [33].
  • Altogether, our data show that Plg/Pla regulates alpha-ENO expression through the MEK/ERK pathway [32].

Other interactions of Plg


Analytical, diagnostic and therapeutic context of Plg

  • Neither native nor variant plasminogen mRNA nor translation products could be identified by Northern or Western blot of liver extracts from Plg-/- mice [4].
  • Recent gene targeting studies indicate that the plasminogen system is implicated in cell migration and matrix degradation during arterial neointima formation and atherosclerotic aneurysm formation [14].
  • Here we show, based on optical biosensor analyses, that immobilized HRG interacts with soluble plasminogen with high affinity and with an extremely slow dissociation rate [36].
  • METHODS: RT-PCR was used to detect gene expression for plasminogen activators and their inhibitors in naïve and immunized mice [37].
  • These findings indicate that several interactions that have been described between these MMPs and the plasminogen/plasmin system in a purified system do not significantly affect plasmin-mediated cellular fibrinolytic activity under cell culture conditions [38].


  1. Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. Bugge, T.H., Flick, M.J., Daugherty, C.C., Degen, J.L. Genes Dev. (1995) [Pubmed]
  2. Synergy between a plasminogen cascade and MMP-9 in autoimmune disease. Liu, Z., Li, N., Diaz, L.A., Shipley, M., Senior, R.M., Werb, Z. J. Clin. Invest. (2005) [Pubmed]
  3. Pancreas recovery following cerulein-induced pancreatitis is impaired in plasminogen-deficient mice. Lugea, A., Nan, L., French, S.W., Bezerra, J.A., Gukovskaya, A.S., Pandol, S.J. Gastroenterology (2006) [Pubmed]
  4. Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Ploplis, V.A., Carmeliet, P., Vazirzadeh, S., Van Vlaenderen, I., Moons, L., Plow, E.F., Collen, D. Circulation (1995) [Pubmed]
  5. Drug dependence, synaptic plasticity, and tissue plasminogen activator. Yamada, K., Nagai, T., Nabeshima, T. J. Pharmacol. Sci. (2005) [Pubmed]
  6. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Dong, Z., Kumar, R., Yang, X., Fidler, I.J. Cell (1997) [Pubmed]
  7. Plasminogen is required for efficient dissemination of B. burgdorferi in ticks and for enhancement of spirochetemia in mice. Coleman, J.L., Gebbia, J.A., Piesman, J., Degen, J.L., Bugge, T.H., Benach, J.L. Cell (1997) [Pubmed]
  8. Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency. Bugge, T.H., Kombrinck, K.W., Flick, M.J., Daugherty, C.C., Danton, M.J., Degen, J.L. Cell (1996) [Pubmed]
  9. Plasminogen mRNA induction in the mouse brain after kainate excitation: codistribution with plasminogen activator inhibitor-2 (PAI-2) mRNA. Sharon, R., Abramovitz, R., Miskin, R. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  10. The development of bleomycin-induced pulmonary fibrosis in mice deficient for components of the fibrinolytic system. Swaisgood, C.M., French, E.L., Noga, C., Simon, R.H., Ploplis, V.A. Am. J. Pathol. (2000) [Pubmed]
  11. Plasminogen activators promote excitotoxicity-induced retinal damage. Mali, R.S., Cheng, M., Chintala, S.K. FASEB J. (2005) [Pubmed]
  12. Aging accelerates endotoxin-induced thrombosis : increased responses of plasminogen activator inhibitor-1 and lipopolysaccharide signaling with aging. Yamamoto, K., Shimokawa, T., Yi, H., Isobe, K., Kojima, T., Loskutoff, D.J., Saito, H. Am. J. Pathol. (2002) [Pubmed]
  13. NS-398 inhibits tumor growth and liver metastasis of colon cancer through induction of apoptosis and suppression of the plasminogen activation system in a mouse model. Nishikawa, M., Stapleton, P.P., Freeman, T.A., Gaughan, J.P., Matsuda, T., Daly, J.M. J. Am. Coll. Surg. (2004) [Pubmed]
  14. Reduced transplant arteriosclerosis in plasminogen-deficient mice. Moons, L., Shi, C., Ploplis, V., Plow, E., Haber, E., Collen, D., Carmeliet, P. J. Clin. Invest. (1998) [Pubmed]
  15. The effects of intrinsic pathway protease deficiencies on plasminogen-deficient mice. Cheng, Q., Zhao, Y., Lawson, W.E., Polosukhin, V.V., Johnson, J.E., Blackwell, T.S., Gailani, D. Blood (2005) [Pubmed]
  16. Plasmin activity is required for myogenesis in vitro and skeletal muscle regeneration in vivo. Suelves, M., López-Alemany, R., Lluís, F., Aniorte, G., Serrano, E., Parra, M., Carmeliet, P., Muñoz-Cánoves, P. Blood (2002) [Pubmed]
  17. Regulation of gelatinase activity in mice with targeted inactivation of components of the plasminogen/plasmin system. Lijnen, H.R., Silence, J., Lemmens, G., Frederix, L., Collen, D. Thromb. Haemost. (1998) [Pubmed]
  18. Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice. Lund, L.R., Green, K.A., Stoop, A.A., Ploug, M., Almholt, K., Lilla, J., Nielsen, B.S., Christensen, I.J., Craik, C.S., Werb, Z., Danø, K., Rømer, J. EMBO J. (2006) [Pubmed]
  19. Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Pawlak, R., Rao, B.S., Melchor, J.P., Chattarji, S., McEwen, B., Strickland, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  20. Plasminogen Activator Inhibitor Type-1-Deficient Mice Have an Enhanced IFN-{gamma} Response to Lipopolysaccharide and Staphylococcal Enterotoxin B. Renckens, R., Pater, J.M., Poll, T. J. Immunol. (2006) [Pubmed]
  21. A plasminogen-like protein selectively degrades stearoyl-CoA desaturase in liver microsomes. Heinemann, F.S., Korza, G., Ozols, J. J. Biol. Chem. (2003) [Pubmed]
  22. Functional corpora lutea are formed in matrix metalloproteinase inhibitor-treated plasminogen-deficient mice. Wahlberg, P., Bodén, I., Paulsson, J., Lund, L.R., Liu, K., Ny, T. Endocrinology (2007) [Pubmed]
  23. Genetic polymorphism of murine tissue plasminogen activator associated with antiphospholipid syndrome. Shirai, J., Ida, A., Jiang, Y., Sanokawa-Akakura, R., Miura, Y., Yan, K., Hamano, Y., Hirose, S., Shirai, T. Genes Immun. (1999) [Pubmed]
  24. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). Lee, C.G., Homer, R.J., Zhu, Z., Lanone, S., Wang, X., Koteliansky, V., Shipley, J.M., Gotwals, P., Noble, P., Chen, Q., Senior, R.M., Elias, J.A. J. Exp. Med. (2001) [Pubmed]
  25. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation. Tarui, T., Akakura, N., Majumdar, M., Andronicos, N., Takagi, J., Mazar, A.P., Bdeir, K., Kuo, A., Yarovoi, S.V., Cines, D.B., Takada, Y. Thromb. Haemost. (2006) [Pubmed]
  26. Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice. Mueller, B.M., Yu, Y.B., Laug, W.E. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  27. The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin. Osterwalder, T., Cinelli, P., Baici, A., Pennella, A., Krueger, S.R., Schrimpf, S.P., Meins, M., Sonderegger, P. J. Biol. Chem. (1998) [Pubmed]
  28. Urokinase-type plasminogen activator potentiates lipopolysaccharide-induced neutrophil activation. Abraham, E., Gyetko, M.R., Kuhn, K., Arcaroli, J., Strassheim, D., Park, J.S., Shetty, S., Idell, S. J. Immunol. (2003) [Pubmed]
  29. Modulation of murine B16F10 melanoma plasminogen activator production by a synthetic peptide derived from the laminin A chain. Stack, M.S., Gray, R.D., Pizzo, S.V. Cancer Res. (1993) [Pubmed]
  30. Restoration of thrombolytic potential in plasminogen-deficient mice by bolus administration of plasminogen. Lijnen, H.R., Carmeliet, P., Bouché, A., Moons, L., Ploplis, V.A., Plow, E.F., Collen, D. Blood (1996) [Pubmed]
  31. Plasminogen directs the pleiotropic effects of uPA in liver injury and repair. Currier, A.R., Sabla, G., Locaputo, S., Melin-Aldana, H., Degen, J.L., Bezerra, J.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  32. Plasminogen/plasmin regulates alpha-enolase expression through the MEK/ERK pathway. Sousa, L.P., Silva, B.M., Brasil, B.S., Nogueira, S.V., Ferreira, P.C., Kroon, E.G., Kato, K., Bonjardim, C.A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  33. Plasminogen-induced IL-1beta and TNF-alpha production in microglia is regulated by reactive oxygen species. Min, K.J., Jou, I., Joe, E. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  34. The plasminogen activator inhibitor PAI-1 controls in vivo tumor vascularization by interaction with proteases, not vitronectin. Implications for antiangiogenic strategies. Bajou, K., Masson, V., Gerard, R.D., Schmitt, P.M., Albert, V., Praus, M., Lund, L.R., Frandsen, T.L., Brunner, N., Dano, K., Fusenig, N.E., Weidle, U., Carmeliet, G., Loskutoff, D., Collen, D., Carmeliet, P., Foidart, J.M., Noël, A. J. Cell Biol. (2001) [Pubmed]
  35. Plasminogen mediates the pathological effects of urokinase-type plasminogen activator overexpression. Bolon, I., Zhou, H.M., Charron, Y., Wohlwend, A., Vassalli, J.D. Am. J. Pathol. (2004) [Pubmed]
  36. Plasminogen is tethered with high affinity to the cell surface by the plasma protein, histidine-rich glycoprotein. Jones, A.L., Hulett, M.D., Altin, J.G., Hogg, P., Parish, C.R. J. Biol. Chem. (2004) [Pubmed]
  37. Plasminogen Activators and Inhibitors in the Corneas of Mice Infected with Pseudomonas aeruginosa. Berk, R.S., Katar, M., Dong, Z., Day, D.E. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  38. Matrix metalloproteinase deficiencies do not impair cell-associated fibrinolytic activity. Ugwu, F., Lemmens, G., Collen, D., Lijnen, H.R. Thromb. Res. (2001) [Pubmed]
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