Placenta
Volume 30, Issue 12 , Pages 1045-1051 , December 2009

Hypoxia Enhances FGF2- and VEGF-Stimulated Human Placental Artery Endothelial Cell Proliferation: Roles of MEK1/2/ERK1/2 and PI3K/AKT1 Pathways

  • K. Wang

      Affiliations

    • Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, USA
    • ,
  • Y.-z. Jiang

      Affiliations

    • Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, USA
    • ,
  • D.-b. Chen

      Affiliations

    • Department of Obstetrics and Gynecology, University of California, Irvine, CA 92697, USA
    • ,
  • J. Zheng

      Affiliations

    • Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, USA
    • Corresponding Author InformationCorresponding author at: Department of Obstetrics and Gynecology, University of Wisconsin, PAB1, Meriter Hospital, 202 S. Park St., Madison, WI 53715. Tel.: +1 608 417 6314; fax:+1 608 257 1304.

,Accepted 15 October 2009.

References 

  1. Rosenfeld CR, Morriss FH, Makowski El, Meschia G, Battaglia FC. Circulatory changes in the reproductive tissues of ewes during pregnancy. Gynecol Invest. 1974;5:252–268
  2. Alexander G. Birth weight of lambs: influences and consequences. In:  Elliott K,  Knight J editor. Ciba foundation symposium 27: size at birth. New York: Elsevier; 1974;p. 215–245
  3. Reynolds LP, Redmer DA. Utero-placental vascular development and placental function. J Anim Sci. 1995;73:1839–1851
  4. Genbacev O, Zhou Y, Ludlow JW, Fisher SJ. Regulation of human placental development by oxygen tension. Science. 1997;277:1669–1672
  5. Jauniaux E, Watson AL, Hempstock J, Bao Y-P, Skepper JN, Burton GJ. Onset of maternal arterial blood flow and placental oxidative stress: a possible factor in human early pregnancy failure. Am J Pathol. 2000;157:2111–2122
  6. Jauniaux E, Poston L, Burton GJ. Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Hum Reprod Update. 2006;12:747–755
  7. Zygmunt M, Herr F, Munstedt K, Lang U, Liang OD. Angiogenesis and vasculogenesis in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2003;110:S10–S18
  8. Magness RR, Zheng J. Circulatory changes during gestation. In:  Gluckman PD,  Heymann MA editor. Scientific basis of pediatric and perinatal medicine. London: Edward Arnold Publishers; 1996;p. 762–772
  9. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–676
  10. Zheng J, Bird IM, Chen DB, Magness RR. Angiotensin II regulation of fetoplacental artery endothelial functions. J Physiol (London). 2005;565:59–69
  11. Red-Horse K, Zhou Y, Genbacev O, Prakobphol A, Foulk R, McMaster M, et al. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J Clin Invest. 2004;114:744–754
  12. Meininger CJ, Schelling ME, Granger HJ. Adenosine and hypoxia stimulate proliferation and migration of endothelial cells. Am J Physiol. 1988;255:H554–562
  13. Tucci M, Hammerman SI, Furfaro S, Saukonnen JJ, Conca TJ, Farber HW. Distinct effect of hypoxia on endothelial cell proliferation and cycling. Am J Physiol. 1997;272:C1700–1708
  14. Schäfer M, Ewald N, Schafer C, Stapler A, Piper HM, Noll T. Signaling of hypoxia-induced autonomous proliferation of endothelial cells. FASEB J. 2003;17:449–451
  15. Humar R, Kiefer FN, Berns H, Resink TJ, Battegay EJ. Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR)-dependent signaling. FASEB J. 2002;16:771–780
  16. Li W, Petrimpol M, Molle KD, Hall MN, Battegay EJ, Humar R. Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2. Circ Res. 2007;100:79–87
  17. Phillips PG, Birnby LM, Narendran A. Hypoxia induces capillary network formation in cultured bovine pulmonary microvessel endothelial cells. Am J Physiol. 1995;268:L789–800
  18. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003;9:677–684
  19. Shreeniwas R, Ogawa S, Cozzolino F, Torcia G, Braunstein N, Butura C, et al. Macrovascular and microvascular endothelium during long-term hypoxia: alterations in cell growth, monolayer permeability, and cell surface coagulant properties. J Cell Physiol. 1991;146:8–17
  20. Oosthuyse B, Moons L, Storkebaum E, Beck H, Nuyens D, Brusselmans K, et al. Deletion of the hypoxiaresponse element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet. 2001;28:131–138
  21. Byrne AM, Bouchier-Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med. 2005;9:777–794
  22. Dailey L, Ambrosetti D, Mansukhani A, Basilico C. Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev. 2005;16:233–247
  23. Powers CJ, McLeskey SW, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endo-related Cancer. 2000;7:165–197
  24. Zheng J, Wen Y, Song Y, Wang K, Chen DB, Magness RR. Activation of multiple signaling pathways is critical for fibroblast growth factor 2- and vascular endothelial growth factor-stimulated ovine fetoplacental endothelial cell proliferation. Biol Reprod. 2008;78:143–150
  25. Mata-Greenwood E, Liao WX, Zheng J, Chen DB. Differential activation of multiple signalling pathways dictates eNOS upregulation by FGF2 but not VEGF in placental artery endothelial cells. Placenta. 2008;29:708–717
  26. Zheng J, Bird IM, Melsaether AN, Magness RR. Activation of the mitogen-activated protein kinase cascade is necessary but not sufficient for basic fibroblast growth factor- and epidermal growth factor-stimulated expression of endothelial nitric oxide synthase in ovine fetoplacental artery endothelial cells. Endocrinology. 1999;140:1399–1407
  27. Risbud MV, Guttapalli A, Albert TJ, Shapiro IM. Hypoxia activates MAPK activity in rat nucleus pulposus cells: regulation of integrin expression and cell survival. Spine. 2005;30:2503–2509
  28. Minet E, Arnould T, Michel G, Roland I, Mottet D, Raes M, et al. Michiels C.ERK activation upon hypoxia: involvement in HIF-1 activation. FEBS Lett. 2000;468:53–58
  29. Gerasimovskaya EV, Tucker DA, Stenmark KR. Activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin is necessary for hypoxia-induced pulmonary artery adventitial fibroblast proliferation. J Appl Physiol. 2005;98:722–731
  30. Das M, Bouchey DM, Moore MJ, Hopkins DC, Nemenoff RA, Stenmark KR. Hypoxia-induced proliferative response of vascular adventitial fibroblasts is dependent on G protein-mediated activation of mitogen-activated protein kinases. J Biol Chem. 2001;276:15631–15640
  31. Campbell JS, Seger R, Graves JD, Graves LM, Jensen AM, Krebs EG. The MAP kinase cascade. Recent Prog Horm Res. 1995;50:131–159
  32. Zheng J, Wen YX, Austin JL, Chen DB. Exogenous nitric oxide stimulates cell proliferation via activation of a mitogen activated protein kinase pathway in ovine fetoplacental artery endothelial cells. Biol Reprod. 2006;74:375–382
  33. Wang K, Song Y, Chen DB, Zheng J. Protein phosphatase 3 differentially modulates vascular endothelial growth factor- and fibroblast growth factor 2-stimulated cell proliferation and signaling in ovine fetoplacental artery endothelial cells. Biol Reprod. 2008;79:704–710
  34. Olszewska-Pazdrak B, Hein TW, Olszewska P, Carney DH. Chronic hypoxia attenuates VEGF signaling and angiogenic responses by downregulation of KDR in human endothelial cells. Am J Physiol Cell Physiol. 2009;296:C1162–1170
  35. Jin N, Hatton N, Swartz DR, Xia X, Harrington MA, Larsen SH, et al. Hypoxia activates jun-N-terminal kinase, extracellular signal-regulated protein kinase, and p38 kinase in pulmonary arteries. Am J Respir Cell Mol Biol. 2000;23:593–601
  36. Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, Dixit V, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem. 1998;273:30336–30343
  37. Zubilewicz A, Hecquet C, Jeanny JC, Soubrane G, Courtois Y, Mascarelli F. Two distinct signalling pathways are involved in FGF2-stimulated proliferation of choriocapillary endothelial cells: a comparative study with VEGF. Oncogene. 2001;20:1403–1413
  38. Crawley JB, Willcocks J, Foxwell BM. Interleukin-7 induces T cell proliferation in the absence of Erk/MAP kinase activity. Eur J Immunol. 1996;26:2717–2723
  39. Liao WX, Feng L, Zhang H, Zheng J, Moore TR, Chen DB. Compartmentalizing VEGF-induced ERK2/1 signaling in placental artery endothelial cell caveolae: a paradoxical role of caveolin-1 in placental angiogenesis in vitro. Mol Endocrinol. 2009;23:1428–1444

☆ This work was supported in part by the National Institutes of Health grants HL64703 and HD38843 (JZ) and HL74947 & HL70562 (DBC).

PII: S0143-4004(09)00330-0

doi: 10.1016/j.placenta.2009.10.007

Placenta
Volume 30, Issue 12 , Pages 1045-1051 , December 2009

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