Analysis of the innate immune receptor NOD1 and its ligands as a novel cause for the development of the intrauterine fetal growth restriction

• Project/Area Number: 24659509
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Kyushu University
• Principal Investigator: HARA TOSHIRO 九州大学, 医学(系)研究科(研究院), 教授 (40150445)
• Co-Investigator(Kenkyū-buntansha): NISHIO Hisanori 九州大学, 大学病院, 助教 (00507783) ; NAGATA Hazumu 九州大学, 医学(系)研究科(研究院), 助教 (20570790)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自然免疫 / 子宮内胎児発育遅延 / 子宮内胎児死亡 / Nod1 / 周産期 / 子宮内発育遅延 / 自然免疫受容体 / NOD1

Research Abstract

Nod1 (nucleotide-binding oligomerization domain containing 1) is one of the pattern recognition receptors that play an important role in the induction of innate immune and inflammatory responses. However, little is known regarding the effects of direct activation of Nod1 on fetus or newborn. In this study, we demonstrated that administration of Nod1 ligand to pregnant mice induced intrauterine fetal death and growth restriction. We also found that fetuses were affected by transplacental passage of maternal Nod1 ligand. We examined the role of Nod1 signaling in a fetal mouse with a focus on the development of vasculopathy. Our observation suggests a possible link between Nod1 ligands-mediated activation of the innate immune system in fetus and IUGR and might offer a new strategy to improve the long-term cardiovascular health of IUGR cases.

Research Products

• [Journal Article] Survival and neurodevelopmental outcome of preterm infants born at 22-24 weeks of gestational age. (2014)
  • Author(s): Ochiai M, Kinjo T, Takahata Y, Iwayama M, Abe T, Ihara K, Ohga S, Fukushima K, Kato K, Taguchi T, Hara T
  • Journal Title: Neonatology Volume: 10 Issue: 2 Pages: 79-84
  • DOI: 10.1159/000355818
  • Peer Reviewed / Open Access
• [Journal Article] Perinatal management of preterm premature ruptured membranes affects neonatal prognosis. (2014)
  • Author(s): Fujiwara A, Fukushima K, Inoue H, Takashima T, Nakahara H, Satoh S, Ochiai M, Hara T, Shimokawa M, Kato K.
  • Journal Title: J Perinat Med. Volume: 11 Issue: 4 Pages: 1-7
  • DOI: 10.1515/jpm-2013-0192
  • Peer Reviewed
• [Journal Article] Clinical outcome of extremely low birth weight infants born at GW22-26 : a report from a single institution in Japan (2013)
  • Author(s): Ochiai M, Kinjo T, Takahata Y, Iwayama M, Kenji I, Ohga S, Kotaro F, Wake N, Tagichi T, Hara T.
  • Journal Title: Neonatology Volume: (in press)
• [Journal Article] Serum neutrophil gelatinase-associated lipocalin as a predictor of the development of bronchopulmonary dysplasia in preterm infants (2013)
  • Author(s): Inoue H, Ohga S, Kusuda T, Kitajima J, Kinjo T, Ochiai M, Takahata Y, Honjo S, Hara T
  • Journal Title: Early Hum Dev Volume: 89(6) Issue: 6 Pages: 425-429
  • DOI: 10.1016/j.earlhumdev.2012.12.011
  • Peer Reviewed
• [Journal Article] Tracheal aspirate gene expression of preterm newborns developing bronchopulmonary dysplasia (2012)
  • Author(s): Hikino S, Ohga S T, Kinjo T, Kusuda T, Ochiai M, Inoue H, Honjo S, Ihara K
  • Journal Title: Pediatr Int. Volume: 54(2) Issue: 2 Pages: 208-14
  • DOI: 10.1111/j.1442-200x.2011.03510.x
  • Peer Reviewed
• [Journal Article] Differential transmission and postnatal outcome in triplets with congenital cytomegalovirus infection (2011)
  • Author(s): Kitajima J, Inoue H, Ohga S, Kinjo T, Ochiai M, Yoshida T, Kusuhara K, Hara T
  • Journal Title: Pediatr Development Pathol Volume: (in press) Issue: 2 Pages: 151-155
  • DOI: 10.2350/11-05-1034-cr.1
  • Peer Reviewed
• [Presentation] Innate immunity and infection in the newborn (2013)
  • Author(s): Hara T.
  • Organizer: The 9th Congress of Asian Society for Pediatric Research
  • Place of Presentation: Kuching, Sarawak, Malaysia
• [Presentation] Activation of Nod1-mediated innate immunity accelerates autherogenesis (2013)
  • Author(s): Kanno S, Nishio H, Sueishi K, Hara T.
  • Organizer: Frontiers in Immunology Research 2013 International Conference
  • Place of Presentation: Monte Carlo, Monaco
• [Presentation] Activation of an innate immune receptor, Nod1, accelerates atherogenesis in Apoe-/-mice (2013)
  • Author(s): Hara T, Kanno S, Nishio H.
  • Organizer: 2nd International Conference on Clinical & Cellular Immunology
  • Place of Presentation: Las Vegas, NV, USA
• [Book] 免疫疾患,標準小児科学第8版監修:内山聖編集:原寿郎/高橋孝雄/細井創 (2014)
  • Author(s): 原寿郎
  • Publisher: 医学書院東京(印刷中)