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Effects of recombinant H2 relaxin on the expression of matrix metalloproteinases and tissue inhibitor metalloproteinase in cultured early placental extravillous trophoblasts

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Abstract

Relaxin promotes softening of the uterine cervix and inhibits uterine contractility in rats, mice and pigs. Little information, however, is available about the role of relaxin in humans. In 2002, LGR7 and LGR8 were discovered to be receptors for relaxin and those receptors were identified in the human placenta. Thus, in this study, effects of recombinant H2 (rH2) relaxin on human early placental extravillous trophoblasts (EVTs) were examined. Isolation of EVTs from early placental trophoblasts was performed using the procedures established in our laboratory. After 48-h subculture, the presence of relaxin receptors in cultured EVTs was characterized by RT-PCR and immunoblotting. The cultured EVTs were treated with different doses (0.3–3 ng/ml) of rH2 relaxin for 24 h. The effects of rH2 relaxin on MMP-2, -3, -9 and TIMP-1 mRNAs levels were examined by real-time RT-PCR. RT-PCR and immunoblotting revealed that relaxin receptors are present in early placental EVTs. Treatment with rH2 relaxin increased MMP-2 and -9 mRNAs levels and decreased TIMP-1 mRNA levels in cultured EVTs, whereas rH2 relaxin did not affect MMP-3 mRNA levels. These results suggest that relaxin may promote the invasive potential of early placental EVTs through up-regulating MMP-2, -9 mRNAs and down-regulating TIMP-1 mRNA in EVTs.

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References

  1. V. Sakbun, S.M. Ali, F.C. Greenwood, G.D. Bryant-Greenwood, J. Clin. Endocrinol. Metab. 70, 508–514 (1990)

    Article  CAS  PubMed  Google Scholar 

  2. G.D. Bryant-Greenwood, C. Schwabe, Endocr. Rev. 15, 26 (1994)

    Google Scholar 

  3. X. Qin, J. Garibay-Tupas, P.K. Chua, L. Cachola, G.D. Bryant-Greenwood, Biol. Reprod. 56, 800–811 (1997)

    Article  CAS  PubMed  Google Scholar 

  4. C. Liu, E. Eriste, S. Sutton et al., J. Biol. Chem. 278, 50754–50764 (2003)

    Article  CAS  PubMed  Google Scholar 

  5. C. Binder, T. Hagemann, B. Husen, M. Schulz, A. Einspanier, Mol. Hum. Reprod. 8, 789–796 (2002)

    Article  CAS  PubMed  Google Scholar 

  6. E.N. Unemori, L.B. Pickford, A.L. Salles et al., J. Clin. Invest. 98, 2739–2745 (1996)

    Article  CAS  PubMed  Google Scholar 

  7. S.Y. Hsu, K. Nakabayashi, S. Nishi et al., Science 295, 671–674 (2002)

    Article  CAS  PubMed  Google Scholar 

  8. G.D. Bryant-Greenwood, S.Y. Yamamoto, K.M. Lowndes et al., Ann. NY Acad. Sci. 1041, 338–344 (2005)

    Article  CAS  PubMed  Google Scholar 

  9. R.A. Bathgate, R. Ivell, B.M. Sanborn, O.D. Sherwood, R.J. Summers, Pharmacol. Rev. 58, 7–31 (2006)

    Article  CAS  PubMed  Google Scholar 

  10. S.Y. Hsu, K. Nakabayashi, S. Nishi et al., Mol. Cell. Endocrinol. 202, 165–170 (2003)

    CAS  PubMed  Google Scholar 

  11. L.W. Eddie, R.J. Bell, A. Lester et al., Lancet 1, 1344–1346 (1986)

    Article  CAS  PubMed  Google Scholar 

  12. R.J. Bell, L.W. Eddie, A.R. Lester, E.C. Wood, P.D. Johnston, H.D. Niall, Obstet. Gynecol. 69, 585–589 (1987)

    CAS  PubMed  Google Scholar 

  13. A. Tarrade, F. Goffin, C. Munaut et al., Biol. Reprod. 67, 1628–1637 (2002)

    Article  CAS  PubMed  Google Scholar 

  14. A.Y. Demir-Weusten, Y. Seval, P. Kaufmann, R. Demir, G. Yucel, B. Huppertz, Acta Histochem. 109, 403–412 (2007)

    Article  CAS  PubMed  Google Scholar 

  15. K. Lowndes, A. Amano, S.Y. Yamamoto, G.D. Bryant-Greenwood, Placenta 27, 610–618 (2006)

    Article  CAS  PubMed  Google Scholar 

  16. I. Wiqvist, A. Norstrom, E. O’Byrne, N. Wiqvist, Acta Endocrinol. (Copenh.) 106, 127–132 (1984)

    CAS  Google Scholar 

  17. S. Palejwala, D.E. Stein, G. Weiss, B.P. Monia, D. Tortoriello, L.T. Goldsmith, Endocrinology 142, 3405–3413 (2001)

    Article  CAS  PubMed  Google Scholar 

  18. X. Qin, P.K. Chua, R.H. Ohira, G.D. Bryant-Greenwood, Biol. Reprod. 56, 812–820 (1997)

    Article  CAS  PubMed  Google Scholar 

  19. H. Nishi, K. Ohyashiki, A. Fujito et al., Placenta 20, 317–323 (1999)

    Article  CAS  PubMed  Google Scholar 

  20. C.H. Graham, P.K. Lala, Biochem. Cell Biol. 70, 867–874 (1992)

    Article  CAS  PubMed  Google Scholar 

  21. B. Huppertz, S. Kertschanska, A.Y. Demir, H.G. Frank, P. Kaufmann, Cell Tissue Res. 291, 133–148 (1998)

    Article  CAS  PubMed  Google Scholar 

  22. G.I. Goldberg, A. Strongin, I.E. Collier, L.T. Genrich, B.L. Marmer, J. Biol. Chem. 267, 4583–4591 (1992)

    CAS  PubMed  Google Scholar 

  23. W.G. Stetler-Stevenson, H.C. Krutzsch, L.A. Liotta, J. Biol. Chem. 264, 17374–17378 (1989)

    CAS  PubMed  Google Scholar 

  24. S.J. Fisher, T.Y. Cui, L. Zhang et al., Cell Biol. 109, 891–902 (1989)

    Article  CAS  Google Scholar 

  25. K. Isaka, S. Usuda, H. Ito et al., Placenta 24, 53–64 (2003)

    Article  CAS  PubMed  Google Scholar 

  26. C.L. Librach, Z. Werb, M.L. Fitzgerald et al., J. Cell Biol. 113, 437–449 (1991)

    Article  CAS  PubMed  Google Scholar 

  27. P. Xu, Y.L. Wang, S.J. Zhu, S.Y. Luo, Y.S. Piao, L.Z. Zhuang, Biol. Reprod. 62, 988–994 (2000)

    Article  CAS  PubMed  Google Scholar 

  28. S. Shimonovitz, A. Hurwitz, M. Dushnik, E. Anteby, T. Geva-Eldar, S. Yagel, Am. J. Obstet. Gynecol. 171, 832–838 (1994)

    CAS  PubMed  Google Scholar 

  29. Y. Ogata, J.J. Enghild, H. Nagase, J. Biol. Chem. 267, 3581–3584 (1992)

    CAS  PubMed  Google Scholar 

  30. P. Bischof, Early Pregnancy 5, 30–31 (2001)

    CAS  PubMed  Google Scholar 

  31. N. Oki, H. Matsuo, S. Nakago, H. Murakoshi, J.B. Laoag-Fernandez, T. Maruo, J. Clin. Endocrinol. Metab. 89, 5213–5221 (2004)

    Article  CAS  PubMed  Google Scholar 

  32. E. Staun-Ram, S. Goldman, D. Gabarin, E. Shalev, Reprod. Biol. Endocrinol. 2, 59 (2004)

    Article  PubMed  Google Scholar 

  33. M.D. Abramoff, P.J. Magelhaes, S.J. Ram, Biophotonics Int. 11, 36–42 (2004)

    Google Scholar 

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Acknowledgments

This work was supported in part by the Grants-in-Aid for Scientific Research (No. 16790953 and No. 18791154) from the Japan Society for the Promotion of Science. All authors have nothing to declare. We wish to thank Dr. Elaine Unemori in BAS Medical, CA, for her kind gifts of the recombinant H2 relaxin used in the present study. We also wish to thank Dr Benjamin K. Tsang, University of Ottawa, Ottawa, Canada for his kind gifts of the HTR-8/SV neo trophoblast cells.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuoku, Kobe, 650-0017, Japan

    Nobuyuki Maruo, Koji Nakabayashi, Senn Wakahashi, Ai Yata & Takeshi Maruo

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  1. Nobuyuki Maruo
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  2. Koji Nakabayashi
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  3. Senn Wakahashi
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  4. Ai Yata
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  5. Takeshi Maruo
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Correspondence to Takeshi Maruo.

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Maruo, N., Nakabayashi, K., Wakahashi, S. et al. Effects of recombinant H2 relaxin on the expression of matrix metalloproteinases and tissue inhibitor metalloproteinase in cultured early placental extravillous trophoblasts. Endocr 32, 303–310 (2007). https://doi.org/10.1007/s12020-008-9034-5

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  • DOI: https://doi.org/10.1007/s12020-008-9034-5

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