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Gene Review

Plau  -  plasminogen activator, urokinase

Rattus norvegicus

Synonyms: U-plasminogen activator, Urokinase-type plasminogen activator, uPA
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Disease relevance of Plau

  • Our results indicated that altered expression of PAI-1, uPA, and uPAR in diabetic nephropathy was associated with mesangial expansion and that the beneficial effects of ACE-I may be at least associated with such expression [1].
  • Urokinase plasminogen activator (uPA) is a serine protease which has frequently been implicated in the process of tumor cell invasion and metastasis [2].
  • By contrast, uPA RNA (and enzyme) levels were elevated by up to 70-fold in metastatic clones of dimethylbenz(a)anthracene-induced rat mammary adenocarcinoma (DMBA-8) due to predominantly posttranscriptional mechanisms [2].
  • CONCLUSIONS: We concluded that PG and PL had significant adhesion- and abscess-reducing effects and may act by modulating fibrinolytic capacity of uPA and/or tPA produced from macrophages in a rat peritonitis model [3].
  • These results underscore the utility of anti-proteolytic agents (B-428) in addition to standard hormone therapy (TAM) in advanced breast cancer patients where the uPA/uPAR system plays a key role in tumor progression [4].

Psychiatry related information on Plau


High impact information on Plau


Chemical compound and disease context of Plau


Biological context of Plau

  • The urokinase-type plasminogen activator (uPA) system has been implicated in cell migration, angiogenesis, extracellular matrix synthesis and tissue remodelling [12].
  • DNA synthesis was assessed by measuring the incorporation of [3H]-thymidine into cellular DNA fraction. tPA, uPA and type-1 plasminogen activator inhibitor (PAI-1) gene expressions were measured by Northern blotting [13].
  • These results suggest that in addition to gene transcription, posttranscriptional events localized in the nucleus and cytoplasm are key determinants of uPA gene activation in rat mammary adenocarcinomas [2].
  • Nuclear run-on assays and RNA half-life estimations indicated that metastatic MAT 13762 rat mammary adenocarcinoma cells expressed 3.5-fold higher levels of uPA RNA than a nonmetastatic derivative (J-clone), due to a combined increase in uPA gene transcription and cytoplasmic RNA stability [2].
  • Whereas uPA transcript and protein levels were highest at the earliest stage of follicular growth examined and decreased markedly before the expected time of ovulation, the opposite was true for uPAR [14].

Anatomical context of Plau

  • Interestingly, uninjured control tendons expressed uPA mRNA and protein, but little uPAR transcripts and protein [12].
  • On day 14 following Achilles tendon division, uPA receptor protein increased 12.6-fold (p<0.001) while uPA itself increased only 1.3-fold (p<0.05) [12].
  • Diabetic rats exhibited high levels of expression of PAI-1, uPA, and uPAR mRNAs and type IV collagen protein, mainly in mesangial cells [1].
  • Moreover, treatment of nonmetastatic DMBA-8 cell lines with protein synthesis inhibitors led to an increase in nuclear and cytoplasmic uPA RNA levels, without altering the rate of uPA gene transcription [2].
  • Urokinase plasminogen activator (uPA) has been implicated in the healing responses of injured arteries, but the importance of its various properties that influence smooth muscle cell (SMC) proliferation and migration in vivo is unclear [15].

Associations of Plau with chemical compounds

  • The mRNA and activities of both urokinase-type PA (uPA) and tissue-type PA (tPA) were enhanced by PGE2 treatment [16].
  • Proximal tubules freshly isolated from rats treated for 2 d with lovastatin (4 mg/kg per d) showed increased tissue-type plasminogen activator (tPA) and urokinase (uPA) activities and antigens [17].
  • Proteolytically inactive r-uPA/H/Q (containing glutamine rather than histidine-204 in its catalytic site) did not affect neointima or lumen size [15].
  • Using a model in which surgical partial hepatectomy is combined with feeding of 2-acetylaminofluorene (2-AAF) to induce liver regeneration by proliferation and differentiation of oval cells, expression of uPA, uPAR, and PAI-1 was detected by immunohistochemistry mainly in the duct-like formations of expanding oval cells [18].
  • Following ovulation, uPA mRNA was expressed in capillary sprouts within the developing corpus luteum [19].

Regulatory relationships of Plau


Other interactions of Plau


Analytical, diagnostic and therapeutic context of Plau

  • We used a rat Achilles tendon model to study mRNA and protein expression of uPA and its receptor (uPAR) during tendon healing using immunohistochemical, Northern and Western blot analyses [12].
  • We have now documented the de novo appearance of active uPA in livers from male Fischer F344 rats that underwent 70% partial hepatectomy (PHx) as early as 1 minute after surgery [24].
  • Using in situ hybridization, we detected uPA mRNA in the ovary along the route of capillary extension, originating at the existing ovarian vasculature, extending toward growing follicles, and terminating at the newly formed capillary sheaths surrounding each growing follicle [19].
  • In untreated animals both tPA and urokinase-type plasminogen activator (uPA) activity was significantly increased within the region of infarct by 6 hours after reperfusion [25].
  • Together, these studies demonstrate the ability of anti-uPAR antibody to decrease tumor volume and detect the presence of microscopic occult tumor metastases in malignancies where uPA/uPAR play a key role in tumor progression [26].


  1. Renal synthesis of urokinase type-plasminogen activator, its receptor, and plasminogen activator inhibitor-1 in diabetic nephropathy in rats: modulation by angiotensin-converting-enzyme inhibitor. Kenichi, M., Masanobu, M., Takehiko, K., Shoko, T., Akira, F., Katsushige, A., Takashi, H., Yoshiyuki, O., Shigeru, K. J. Lab. Clin. Med. (2004) [Pubmed]
  2. Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells. Henderson, B.R., Tansey, W.P., Phillips, S.M., Ramshaw, I.A., Kefford, R.F. Cancer Res. (1992) [Pubmed]
  3. Prevention of intraperitoneal adhesions and abscesses by polysaccharides isolated from Phellinus spp in a rat peritonitis model. Bae, J.S., Ahn, S.J., Yim, H., Jang, K.H., Jin, H.K. Ann. Surg. (2005) [Pubmed]
  4. Prevention of breast cancer growth, invasion, and metastasis by antiestrogen tamoxifen alone or in combination with urokinase inhibitor B-428. Xing, R.H., Mazar, A., Henkin, J., Rabbani, S.A. Cancer Res. (1997) [Pubmed]
  5. In vivo gene delivery of urokinase-type plasminogen activator with regulatable lentivirus induces behavioural changes in chronic cocaine administration. Bahi, A., Boyer, F., Gumy, C., Kafri, T., Dreyer, J.L. Eur. J. Neurosci. (2004) [Pubmed]
  6. Nonoxidative ethanol metabolites alter extracellular matrix protein content in rat pancreas. Lugea, A., Gukovsky, I., Gukovskaya, A.S., Pandol, S.J. Gastroenterology (2003) [Pubmed]
  7. Mouse ovarian granulosa cells produce urokinase-type plasminogen activator, whereas the corresponding rat cells produce tissue-type plasminogen activator. Canipari, R., O'Connell, M.L., Meyer, G., Strickland, S. J. Cell Biol. (1987) [Pubmed]
  8. Comparison of intraperitoneal anti-adhesive polysaccharides derived from Phellinus mushrooms in a rat peritonitis model. Bae, J.S., Jang, K.H., Jin, H.K. World J. Gastroenterol. (2005) [Pubmed]
  9. Dexamethasone decreases urokinase plasminogen activator mRNA stability in MAT 13762 rat mammary carcinoma cells. Henderson, B.R., Kefford, R.F. Br. J. Cancer (1993) [Pubmed]
  10. An amino-terminal fragment of urokinase isolated from a prostate cancer cell line (PC-3) is mitogenic for osteoblast-like cells. Rabbani, S.A., Desjardins, J., Bell, A.W., Banville, D., Mazar, A., Henkin, J., Goltzman, D. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  11. Production of pro- and anti-fibrotic agents by rat Kupffer cells; the effect of octreotide. Xidakis, C., Ljumovic, D., Manousou, P., Notas, G., Valatas, V., Kolios, G., Kouroumalis, E. Dig. Dis. Sci. (2005) [Pubmed]
  12. Expression of urokinase-type plasminogen activator and its receptor is up-regulated during tendon healing. Xia, W., de Bock, C., Murrell, G.A., Wang, Y. J. Orthop. Res. (2003) [Pubmed]
  13. Plasminogen activator-plasmin system potentiates the proliferation of hepatocytes in primary culture. Akao, M., Hasebe, Y., Okumura, N., Hagiwara, H., Seki, T., Ariga, T. Thromb. Res. (2002) [Pubmed]
  14. Expression of urokinase-type plasminogen activator and its receptor during ovarian follicular development. Li, M., Karakji, E.G., Xing, R., Fryer, J.N., Carnegie, J.A., Rabbani, S.A., Tsang, B.K. Endocrinology (1997) [Pubmed]
  15. Urokinase plasminogen activator augments cell proliferation and neointima formation in injured arteries via proteolytic mechanisms. Plekhanova, O., Parfyonova, Y., Bibilashvily, R., Domogatskii, S., Stepanova, V., Gulba, D.C., Agrotis, A., Bobik, A., Tkachuk, V. Atherosclerosis (2001) [Pubmed]
  16. Prostaglandin E2 regulates production of plasminogen activator isoenzymes, urokinase receptor, and plasminogen activator inhibitor-1 in primary cultures of rat calvarial osteoblasts. Allan, E.H., Martin, T.J. J. Cell. Physiol. (1995) [Pubmed]
  17. Lovastatin modulates in vivo and in vitro the plasminogen activator/plasmin system of rat proximal tubular cells: role of geranylgeranylation and Rho proteins. Essig, M., Vrtovsnik, F., Nguyen, G., Sraer, J.D., Friedlander, G. J. Am. Soc. Nephrol. (1998) [Pubmed]
  18. Modulation of the plasminogen activator/plasmin system in rat liver regenerating by recruitment of oval cells. Bisgaard, H.C., Santoni-Rugiu, E., Nagy, P., Thorgeirsson, S.S. Lab. Invest. (1998) [Pubmed]
  19. In vivo patterns of expression of urokinase and its inhibitor PAI-1 suggest a concerted role in regulating physiological angiogenesis. Bacharach, E., Itin, A., Keshet, E. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  20. Urokinase-induced smooth muscle cell responses require distinct signaling pathways: a role for the epidermal growth factor receptor. Nicholl, S.M., Roztocil, E., Davies, M.G. J. Vasc. Surg. (2005) [Pubmed]
  21. Follicular stage-dependent regulation of rat granulosa cell plasminogen activator system by transforming growth factor-alpha in vitro. Karakji, E.G., Tsang, B.K. Biol. Reprod. (1995) [Pubmed]
  22. Intestinal transformation results in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions. Berger, D.H., O'Mahony, C.A., Sheng, H., Shao, J., Albo, D., DuBois, R.N., Beauchamp, R.D. Surgery (2003) [Pubmed]
  23. Differences in the implantation rates of rat embryos developed in vivo and in vitro: possible role for plasminogen activators. Aflalo, E.D., Sod-Moriah, U.A., Potashnik, G., Har-Vardi, I. Fertil. Steril. (2004) [Pubmed]
  24. Immediate early detection of urokinase receptor after partial hepatectomy and its implications for initiation of liver regeneration. Mars, W.M., Liu, M.L., Kitson, R.P., Goldfarb, R.H., Gabauer, M.K., Michalopoulos, G.K. Hepatology (1995) [Pubmed]
  25. Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis. Yepes, M., Sandkvist, M., Wong, M.K., Coleman, T.A., Smith, E., Cohan, S.L., Lawrence, D.A. Blood (2000) [Pubmed]
  26. Urokinase receptor antibody can reduce tumor volume and detect the presence of occult tumor metastases in vivo. Rabbani, S.A., Gladu, J. Cancer Res. (2002) [Pubmed]
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