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Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway

  • Authors:
    • Songshan Ye
    • Bingyu Mao
    • Lei Yang
    • Weiyun Fu
    • Junran Hou
  • View Affiliations / Copyright

    Affiliations: Department of Medical Experimental Center, Zhang Zhongjing Traditional Chinese Medicine College, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China
    Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4593-4598
    |
    Published online on: April 15, 2016
       https://doi.org/10.3892/mmr.2016.5146
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Abstract

Paeoniflorin, the major component of Paeonia lactiflora pall, has previously been reported to prevent thrombosis. Plasminogen activator urokinase (uPA) is a serine protease that markedly facilitates normal thrombosis resolution. Paeoniflorin and uPA have been linked to the mitogen‑activated protein kinase (MAPK) signaling pathway. In the current study, the influence of paeoniflorin on the expression of uPA was investigated and the underlying regulatory mechanism was preliminarily determined. The prothrombotic state of the model animals treated with paeoniflorin were assessed by enzyme‑linked immunosorbent assay (ELISA). Additionally, the cytotoxicity of paeoniflorin on human umbilical vein endothelial cell (HUVEC) cultures was estimated using a methyl thiazolyl tetrazolium assay and the possible pathways involved in the interaction between paeoniflorin and uPA were evaluated using western blot analysis. The ELISA results demonstrated that the levels of 6‑keto prostaglandin F1a, fibronectin and uPA were significantly upregulated by treatment with paeoniflorin compared with control (P<0.05). By contrast, the expression of fibrinogen, D‑dimer and thromboxane B2 were inhibited. With an increase in the concentration of paeoniflorin the cell viability of HUVECs decreased gradually. The results of western blot analysis demonstrated that paeoniflorin increased the phosphorylation of MAPK 14 (p38) and MAPK 8 (JNK). The present study demonstrated that paeoniflorin has the potential to improve the prethrombotic state and recanalize thrombosis by increasing the expression of uPA, which may be mediated via regulation of the p38 and JNK MAPK signaling pathways. However, this treatment effect was dependent on the concentration of paeoniflorin used, an unsuitable concentration of the agent would result in a negative effect on the anti‑thrombosis pathways.
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1 

Italiano JE, Patel-Hett S and Hartwig JH: Mechanics of proplatelet elaboration. J Thromb Haemost. 5(Suppl 1): S18–S23. 2007. View Article : Google Scholar

2 

Bender M, Eckly A, Hartwig JH, Elvers M, Pleines I, Gupta S, Krohne G, Jeanclos E, Gohla A, Gurniak C, et al: ADF/n-cofilin-dependent actin turnover determines platelet formation and sizing. Blood. 116:1767–1775. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Ruggeri ZM: Platelets in atherothrombosis. Nature Med. 8:1227–1234. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Stoll G, Kleinschnitz C and Nieswandt B: Molecular mechanisms of thrombus formation in ischemic stroke: Novel insights and targets for treatment. Blood. 112:3555–3562. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Schrör K: Antiplatelet drugs. A comparative review. Drugs. 50:7–28. 1995. View Article : Google Scholar : PubMed/NCBI

6 

Ni H and Freedman J: Platelets in hemostasis and thrombosis: Role of integrins and their ligands. Transfus Apher Sci. 28:257–264. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Barrett NE, Holbrook L, Jones S, Kaiser WJ, Moraes LA, Rana R, Sage T, Stanley RG, Tucker KL, Wright B and Gibbins JM: Future innovations in anti-platelet therapies. Br J Pharmacol. 154:918–939. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Bird JE, Giancarli MR, Allegretto N, Barbera F, Wong P, Schumacher WA, Ogletree ML and Seiffert D: Prediction of the therapeutic index of marketed anti-coagulants and anti-platelet agents by guinea pig models of thrombosis and hemostasis. Thromb Res. 123:146–158. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Northeast AD, Soo KS, Bobrow LG, Gaffney PJ and Burnand KG: The tissue plasminogen activator and urokinase response in vivo during natural resolution of venous thrombus. J Vasc Surg. 22:573–579. 1995. View Article : Google Scholar : PubMed/NCBI

10 

Singh I, Burnand KG, Collins M, Luttun A, Collen D, Boel-houwer B and Smith A: Failure of thrombus to resolve in urokinase-type plasminogen activator gene-knockout mice: Rescue by normal bone marrow-derived cells. Circulation. 107:869–875. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Gossage JA, Humphries J, Modarai B, Burnand KG and Smith A: Adenoviral urokinase-type plasminogen activator (uPA) gene transfer enhances venous thrombus resolution. J Vasc Surg. 44:1085–1090. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Aguirre Ghiso JA, Alonso DF, Farías EF, Gomez DE and Bal de Kier Joffè E: Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype. Eur J Biochem. 263:295–304. 1999. View Article : Google Scholar : PubMed/NCBI

13 

Blasi F and Carmeliet P: uPAR: A versatile signalling orchestrator. Nat Rev Mol Cell Biol. 3:932–943. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Lee KH, Hyun MS and Kim JR: Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis. Clin Exp Metastasis. 20:499–505. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Liu SQ, Huang JA, Qin MB, Su YJ, Lai MY, Jiang HX and Tang GD: Sphingosine kinase 1 enhances colon cancer cell proliferation and invasion by upregulating the production of MMP-2/9 and uPA via MAPK pathways. Int J Colorectal Dis. 27:1569–1578. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Benasciutti E, Pagès G, Kenzior O, Folk W, Blasi F and Crippa MP: MAPK and JNK transduction pathways can phosphorylate Sp1 to activate the uPA minimal promoter element and endogenous gene transcription. Blood. 104:256–262. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Nizamutdinova IT, Jin YC, Kim JS, Yean MH, Kang SS, Kim YS, Lee JH, Seo HG, Kim HJ and Chang KC: Paeonol and paeoniflorin, the main active principles of Paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats. Planta medica. 74:14–18. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Guo RB, Wang GF, Zhao AP, Gu J, Sun XL and Hu G: Paeoni-florin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses. PLoS One. 7:e497012012. View Article : Google Scholar

19 

National Research Council: Guide for the Care and Use of Laboratory Animals. 8th edition. National Academies Press: Washington, D.C; 1996

20 

Miner J and Hoffhines A: The discovery of aspirin's antithrombotic effects. Tex Heart Inst J. 34:179–186. 2007.PubMed/NCBI

21 

Lijnen HR: Matrix metalloproteinases and cellular fibrinolytic activity. Biochemistry (Mosc). 67:92–98. 2002. View Article : Google Scholar

22 

Burnand KG, Gaffney PJ, McGuinness CL, Humphries J, Quarmby JW and Smith A: The role of the monocyte in the generation and dissolution of arterial and venous thrombi. Cardiovasc Surg. 6:119–125. 1998. View Article : Google Scholar : PubMed/NCBI

23 

Ye J, Duan H, Yang X, Yan W and Zheng X: Anti-thrombosis effect of paeoniflorin: Evaluated in a photochemical reaction thrombosis model in vivo. Planta Med. 67:766–767. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Yoshida A, Nakao S, Kobayashi M and Kobayashi H: Flow-mediated vasodilation and plasma fibronectin levels in preeclampsia. Hypertension. 36:400–404. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Pulkkinen MO, Lehto M, Jalkanen M and Näntö-Salonen K: Collagen types and fibronectin in the uterine muscle of normal and hypertensive pregnant patients. Am J Obstet Gynecol. 149:711–717. 1984. View Article : Google Scholar : PubMed/NCBI

26 

Lowe GD and Rumley A: Use of fibrinogen and fibrin D-dimer in prediction of arterial thrombotic events. Thromb Haemost. 82:667–672. 1999.PubMed/NCBI

27 

Bowen RS, Zhang Y, Gu Y, Lewis DF and Wang Y: Increased phospholipase A2 and thromboxane but not prostacyclin production by placental trophoblast cells from normal and preeclamptic pregnancies cultured under hypoxia condition. Placenta. 26:402–409. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Zhao S, Gu Y, Lewis DF and Wang Y: Predominant basal directional release of thromboxane, but not prostacyclin, by placental trophoblasts from normal and preeclamptic pregnancies. Placenta. 29:81–88. 2008. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Ye S, Mao B, Yang L, Fu W and Hou J: Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway. Mol Med Rep 13: 4593-4598, 2016.
APA
Ye, S., Mao, B., Yang, L., Fu, W., & Hou, J. (2016). Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway. Molecular Medicine Reports, 13, 4593-4598. https://doi.org/10.3892/mmr.2016.5146
MLA
Ye, S., Mao, B., Yang, L., Fu, W., Hou, J."Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway". Molecular Medicine Reports 13.6 (2016): 4593-4598.
Chicago
Ye, S., Mao, B., Yang, L., Fu, W., Hou, J."Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway". Molecular Medicine Reports 13, no. 6 (2016): 4593-4598. https://doi.org/10.3892/mmr.2016.5146
Copy and paste a formatted citation
x
Spandidos Publications style
Ye S, Mao B, Yang L, Fu W and Hou J: Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway. Mol Med Rep 13: 4593-4598, 2016.
APA
Ye, S., Mao, B., Yang, L., Fu, W., & Hou, J. (2016). Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway. Molecular Medicine Reports, 13, 4593-4598. https://doi.org/10.3892/mmr.2016.5146
MLA
Ye, S., Mao, B., Yang, L., Fu, W., Hou, J."Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway". Molecular Medicine Reports 13.6 (2016): 4593-4598.
Chicago
Ye, S., Mao, B., Yang, L., Fu, W., Hou, J."Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway". Molecular Medicine Reports 13, no. 6 (2016): 4593-4598. https://doi.org/10.3892/mmr.2016.5146
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