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Gene Review

Plaur  -  plasminogen activator, urokinase receptor

Rattus norvegicus

Synonyms: Par, Plaur3, U-PAR, Urokinase plasminogen activator surface receptor, uPAR, ...
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Disease relevance of Plaur

  • 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].
  • (U87-MG) and intracranial (SNB19) injections of Ad-uPAR-infected glioma cells did not produce tumors in nude mice [2].
  • In the present study, we have used a syngeneic model of rat breast cancer to directly evaluate the role of uPAR as a diagnostic and therapeutic target in metastatic breast cancer [3].
  • 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 [3].
  • We concluded that the combination of polysaccharides and CMC had significant adhesion- and abscess-reducing effects compared with their single treatment and the effects may act by modifying the fibrinolytic capacity of uPA, uPAR and TNF-alpha produced from activated macrophages in a rat peritonitis model [4].

High impact information on Plaur

  • Both phosphatidylinositol 3,4,5-trisphosphate and the evolutionarily conserved Par complex (comprising Par3, Par6 and an atypical PKC (aPKC) such as PKClambda or PKCzeta) are involved in axon specification [5].
  • UPA, and UPAR, as well as PAI-1 [6].
  • Within 5 days, smooth muscle cells (SMCs) on the luminal surface expressed the mRNA for tissue-type plasminogen activator (TPA), urokinase type plasminogen (UPA), the receptor for UPA (UPAR), and plasminogen activator inhibitor type-1 (PAI-1) [6].
  • Furthermore, 1 min after PHx, but not sham operation, urokinase-type plasminogen activator (u-PA) and u-PA receptor were observed in the immunoprecipitates of c-Met [7].
  • We undertook this study to determine whether the role of u-PA in prostate cancer induced angiogenesis and secondary tumor growth by developing a homologous, immunocompetent in vivo model in which the tumors cells secrete an inhibitor of the murine u-PA receptor [8].

Chemical compound and disease context of Plaur

  • The metastatic subline of a rat pancreatic adenocarcinoma differs from the non-metastasizing subline by overexpression of 5 membrane molecules: CD44 variant isoforms, EpCAM, the tetraspanin D6.1A, an uPAR-related molecule and, as described here, the alpha6beta4 integrin [9].

Biological context of Plaur

  • ATF-uPA transfectants were also markedly less invasive than parental SNB19 cells after injection into the brains of nude mice, suggesting that competitive inhibition of the uPA-uPAR interaction on SNB19 cells by means of transfection with ATF cDNA could be a useful therapeutic strategy for inhibiting tumor progression [10].
  • 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 [11].
  • 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 [12].
  • Together, these results suggest that in the adult hyperglycaemic GK/Par rat facing pancreatectomy, duct-cell proliferation and apoptosis from the common pancreatic duct, main ducts and small ducts were not impaired compared to the Wistar rat [13].
  • The urokinase receptor (uPAR) is a multifunctional molecule involved in pericellular, fibrinolytic, and proteolytic activities, as well as in cell adhesion and chemotaxis and may play a role in the pathogenesis of tissue remodeling occurring during glomerulonephritis [14].

Anatomical context of Plaur

  • These findings show for the first time that uPA, and especially its receptor uPAR, are up-regulated during tendon healing [15].
  • 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) [15].
  • Quiescent endothelial cells did not express TPA, UPA, UPAR, or PAI-1 mRNA [6].
  • These findings demonstrate for the first time the presence of uPAR in ovarian follicles and its developmental expression [11].
  • Furthermore, due to increased uPAR expression, experimental animals developed large metastatic lesions in liver, spleen and lymph nodes [16].

Associations of Plaur with chemical compounds

  • Expression of uPA, uPAR, and PAI-1, as assessed by immunohistochemical and Northern blot analyses, was also observed, when cells located in and in close proximity to the bile epithelial structures were activated to enter DNA-synthesis in response to 2-AAF, and after in vivo infusion of various growth factors [12].
  • This permeability defect was correlated with significant increases in the formation of nitric oxide, lipid peroxides, and the peroxynitrite biomarker nitrotyrosine as well as with increases in the expression of VEGF and uPAR [17].
  • Treatment with a nitric oxide synthase inhibitor (N-omega-nitro-L-arginine methyl ester, 50 mg/kg/day) or peroxynitrite scavenger (uric acid, 160 mg/kg/day) blocked the breakdown in the BRB and prevented the increases in formation of lipid peroxides and tyrosine nitration as well as the increases in expression of VEGF and uPAR [17].
  • In terms of beta-cell function, there is no major intrinsic secretory defect in the prediabetic GK/Par beta-cell, and the lack of beta-cell reactivity to glucose (which reflects multiple intracellular abnormalities), as seen during the adult period when the GK/Par rats are overtly diabetic, represents an acquired defect (perhaps glucotoxicity) [18].
  • Results showed that rats receiving nicotine demonstrated an increase in dendritic length and spine density relative to controls in the NAcc and Cg3 brain areas, but not Par 1 [19].

Other interactions of Plaur

  • In control rats, we detected weak signals for PAI-1, uPA, and uPAR mRNAs in glomeruli [1].
  • Here we present data that correlates a significant decrease in the frequency of ICAM-1 and uPAR expressing tumor cells with the appearance of tumor cells in sites distant from that of the primary tumor [20].
  • In the grafts of diabetic recipients the expression of HGF, uPA and uPAR were delayed, being clearly expressed at day 5 rather than day 3 [21].
  • TGF-beta 1 had no effect on either uPA receptor or PAI-1 in this system [22].
  • Data base searches have revealed a low degree of homology to the receptor for the plasminogen activator (uPAR) [23].

Analytical, diagnostic and therapeutic context of Plaur


  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. Adenovirus-mediated delivery of antisense gene to urokinase-type plasminogen activator receptor suppresses glioma invasion and tumor growth. Mohan, P.M., Chintala, S.K., Mohanam, S., Gladson, C.L., Kim, E.S., Gokaslan, Z.L., Lakka, S.S., Roth, J.A., Fang, B., Sawaya, R., Kyritsis, A.P., Rao, J.S. Cancer Res. (1999) [Pubmed]
  3. 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]
  4. The effect of polysaccharides and carboxymethylcellulose combination to prevent intraperitoneal adhesion and abscess formation in a rat peritonitis model. Bae, J.S., Jin, H.K., Jang, K.H. J. Vet. Med. Sci. (2004) [Pubmed]
  5. The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity. Schwamborn, J.C., Püschel, A.W. Nat. Neurosci. (2004) [Pubmed]
  6. Migration of arterial wall cells. Expression of plasminogen activators and inhibitors in injured rat arteries. Reidy, M.A., Irvin, C., Lindner, V. Circ. Res. (1996) [Pubmed]
  7. Growth factor signal transduction immediately after two-thirds partial hepatectomy in the rat. Stolz, D.B., Mars, W.M., Petersen, B.E., Kim, T.H., Michalopoulos, G.K. Cancer Res. (1999) [Pubmed]
  8. Inhibition of prostate cancer neovascularization and growth by urokinase-plasminogen activator receptor blockade. Evans, C.P., Elfman, F., Parangi, S., Conn, M., Cunha, G., Shuman, M.A. Cancer Res. (1997) [Pubmed]
  9. The association of the tetraspanin D6.1A with the alpha6beta4 integrin supports cell motility and liver metastasis formation. Herlevsen, M., Schmidt, D.S., Miyazaki, K., Zöller, M. J. Cell. Sci. (2003) [Pubmed]
  10. Modulation of invasive properties of human glioblastoma cells stably expressing amino-terminal fragment of urokinase-type plasminogen activator. Mohanam, S., Chandrasekar, N., Yanamandra, N., Khawar, S., Mirza, F., Dinh, D.H., Olivero, W.C., Rao, J.S. Oncogene (2002) [Pubmed]
  11. 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]
  12. 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]
  13. Impaired pancreatic duct-cell growth in focal areas of regeneration after partial pancreatectomy in the adult Goto-Kakizaki rat, a spontaneous model of non-insulin dependent diabetes mellitus. Plachot, C., Portha, B. Histochem. J. (2001) [Pubmed]
  14. Induction of urokinase receptor expression in nephrotoxic nephritis. Xu, Y., Berrou, J., Chen, X., Fouqueray, B., Callard, P., Sraer, J.D., Rondeau, E. Exp. Nephrol. (2001) [Pubmed]
  15. 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]
  16. Overexpression of urokinase receptor in breast cancer cells results in increased tumor invasion, growth and metastasis. Xing, R.H., Rabbani, S.A. Int. J. Cancer (1996) [Pubmed]
  17. Experimental diabetes causes breakdown of the blood-retina barrier by a mechanism involving tyrosine nitration and increases in expression of vascular endothelial growth factor and urokinase plasminogen activator receptor. El-Remessy, A.B., Behzadian, M.A., Abou-Mohamed, G., Franklin, T., Caldwell, R.W., Caldwell, R.B. Am. J. Pathol. (2003) [Pubmed]
  18. beta-cell function and viability in the spontaneously diabetic GK rat: information from the GK/Par colony. Portha, B., Giroix, M.H., Serradas, P., Gangnerau, M.N., Movassat, J., Rajas, F., Bailbe, D., Plachot, C., Mithieux, G., Marie, J.C. Diabetes (2001) [Pubmed]
  19. Nicotine sensitization increases dendritic length and spine density in the nucleus accumbens and cingulate cortex. Brown, R.W., Kolb, B. Brain Res. (2001) [Pubmed]
  20. Decreased expression of intercellular adhesion molecule-1 (ICAM-1) and urokinase-type plasminogen activator receptor (uPAR) is associated with tumor cell spreading in vivo. Donadio, A.C., Remedi, M.M., Frede, S., Bonacci, G.R., Chiabrando, G.A., Pistoresi-Palencia, M.C. Clin. Exp. Metastasis (2002) [Pubmed]
  21. Effects of diabetes and hypoxia on gene markers of angiogenesis (HGF, cMET, uPA and uPAR, TGF-alpha, TGF-beta, bFGF and Vimentin) in cultured and transplanted rat islets. Vasir, B., Reitz, P., Xu, G., Sharma, A., Bonner-Weir, S., Weir, G.C. Diabetologia (2000) [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. Cloning and functional characterization of a new phosphatidyl-inositol anchored molecule of a metastasizing rat pancreatic tumor. Rösel, M., Claas, C., Seiter, S., Herlevsen, M., Zöller, M. Oncogene (1998) [Pubmed]
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