Repair of the damaged trophoblast cells through CD44-mediated signaling

• Project/Area Number: 23592416
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hamamatsu University School of Medicine (2012-2013); Juntendo University (2011)
• Principal Investigator: SUGIMURA Motoi 浜松医科大学, 医学部, 教授 (30273189)
• Co-Investigator(Kenkyū-buntansha): TANAK Toshitaka 順天堂大学, 医学部, 准教授 (30407283) ; MAKINO Shintaro 順天堂大学, 医学部, 准教授 (70570894) ; YORIFUJI Takasi 順天堂大学, 医学部, 助教 (10597058)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 絨毛細胞 / ＣＤ４４ / シグナル伝達 / 再生 / CD44 / sFLT1

Research Abstract

The function of CD44v3 and heparin/heparan sulphate (HS) signaling was investigated during trophoblast cell migration. We evaluated the effect of heparin/ HS/CD44v3-mediated processes during scratch wound closure in TCL-1 cells. An in vitro scratch wound healing assay showed enhanced migration of trophoblast cells in a dose-dependent manner in the presence of heparin compared with controls. Conversely, an anti-CD44 function blocking antibody and CD44siRNA suppressed the migration of trophoblast cells in the presence of heparin in a similar scratch assay. Both heparin treatment and in vitro scratch wounding induced the phosphorylation of p21-activated kinase 1 (PAK1), while the anti-CD44v3 antibody suppressed the heparin-induced phosphorylation of PAK1. These results indicate that heparin/heparan sulphate/CD44v3-mediated signaling, in the absence of growth factor networks, enhances the direct repair of the damaged trophoblast layer through the migration of trophoblast cells.

Research Products

• [Journal Article] Effectiveness of heparin during long-term tocolysis (2013)
  • Author(s): Inagaki T, Makino S, Yorifuji T, Sugimura M, Takeda S
  • Journal Title: ISRN Obstet Gynecol Volume: 27 Pages: 650532-650532
• [Journal Article] Effectiveness of heparin during long-term tocolysis. (2013)
  • Author(s): Inagaki T, MakinoS, yorifuji T, Sugimura M, Takeda S.
  • Journal Title: ISRN Obstet Gynecol. Volume: 2013 Pages: 1-4
  • DOI: 10.1155/2013/650532
  • Peer Reviewed
• [Journal Article] Heparin/heparan sulfate/CD44-v3 enhances cell migration in term placenta-derived immortalized human trophoblast cells (2012)
  • Author(s): Suga N. Sugimura M, Kshiishi T, Yorifuji T, Makino S, Takeda S
  • Journal Title: Biol reprod Volume: 134 Pages: 1-8
• [Journal Article] Heparin/heparan sulfate/CD44-v3 enhances cell migration in term placenta-derived immortalized human trophoblast cells. (2012)
  • Author(s): Suga N. Sugimura M, Kshiishi T, Yorifuji T, Makino S, Takeda S.
  • Journal Title: Biol Reprod. Volume: 134 Issue: 5 Pages: 1-8
  • DOI: 10.1095/biolreprod.111.093690
  • Peer Reviewed
• [Journal Article] Double vertical compression sutures: A novel conservative approach to managing post-partum haemorrhage due to placenta praevia and atonic bleeding. (2012)
  • Author(s): Makino S, tanaka T, Yorifuji T, Koshiishi T, Sugimura M, Takeda S.
  • Journal Title: Aust N Z J Obstet Gynaecol. Volume: 52 Issue: 3 Pages: 290-2
  • DOI: 10.1111/j.1479-828x.2012.01422.x
  • Peer Reviewed