New preventive strategy of bronchopulmonary dysplasia with geranylgeranylacetone

• Project/Area Number: 26870229
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Embryonic/Neonatal medicine
• Research Institution: University of Fukui
• Principal Investigator: Tokuriki Shuko 福井大学, 学術研究院医学系部門, 助教 (60510237)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: heat shock protein / geranylgeranylaceton / premature infant / hyperoxia / alveolarization / 気管支肺異形成 / ゲラニルゲラニルアセトン / heat shock protein 70 / 慢性肺疾患 / 気管支肺異形成症

Outline of Final Research Achievements

We investigated whether geranylgeranylacetone(GGA) protected neonatal lungs from hyperoxic stress in a murine bronchopulmonary dysplasia (BPD) model, and measured serum heat shock protein (HSP)70 levels in preterm humans treated with oxygen. GGA administration enhanced HSP70 expression two-fold compared with normoxia-exposed and vehicle-treated mice. Hyperoxia reduced HSP70 expression, whereas GGA abrogated the effects. Hyperoxia-exposed mice exhibited more apoptotic cells in lung parenchyma and a more simplified alveolar structure with less radial alveolar count (RAC) and larger mean linear intercept (MLI) than normoxia-exposed mice. GGA suppressed the increase in apoptotic cells and the structural changes of the lungs induced by hyperoxia. Serum HSP70 levels of preterm human infants gradually decreased with age.GGA may attenuate hyperoxic injury in neonatal lungs and thereby may prevent the development of BPD.

Research Products

• [Journal Article] Treatment with geranylgeranylacetone induces heat shock protein 70 and attenuates neonatal hyperoxic lung injury in a model of bronchopulmonary dysplasia (2017)
  • Author(s): Shuko Tokuriki, Aiko Igarashi, Takashi Okuno, Genrei Ohta, Hironobu Naiki, Yusei Ohshima
  • Journal Title: Lung Volume: - Issue: 4 Pages: 28447205-28447205
  • DOI: 10.1007/s00408-017-0007-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Postnatal changes in humerus cortical bone thickness reflect the development of metabolic bone disease in preterm infants (2016)
  • Author(s): Shuko Tokuriki, Aiko Igarashi, Takashi Okuno, Genrei Ohta, Takuya Kosaka, Yusei Ohshima
  • Journal Title: Disease Markers Volume: 2016 Pages: 2176594-2176594
  • DOI: 10.1155/2016/2176594
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent Development of Bronchopulmonary Dysplasia (2015)
  • Author(s): Shuko Tokuriki, Takashi Okuno, Genrei Ohta, Yusei Ohshima
  • Journal Title: Disease Markers Volume: 2015 Pages: 620921-620921
  • DOI: 10.1155/2015/620921
  • Peer Reviewed / Open Access
• [Presentation] 新生児慢性肺疾患モデルマウスにおけるgeranylgeranylacetoneの肺傷害防御効果 (2016)
  • Author(s): 徳力周子 奥野貴士 五十嵐愛子 巨田元礼 大嶋勇成
  • Organizer: 第52回日本周産期・新生児医学会学術集会
  • Place of Presentation: 富山市
  • Year and Date: 2016-07-16