Mechanism of pulmonary fibrosis induced by deranged fatty acid composition

• Project/Area Number: 16K15456
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Gunma University
• Principal Investigator: Kurabayashi Masahiko 群馬大学, 大学院医学系研究科, 教授 (00215047)
• Co-Investigator(Kenkyū-buntansha): 前野 敏孝 群馬大学, 医学部附属病院, 講師 (00436297)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 脂肪酸 / サーファクタント / 線維化 / 肺気腫 / 飽和脂肪酸 / 血管平滑筋 / 肺線維症 / 肺胞上皮細胞 / 肺線維化 / 肺胞上皮

Outline of Final Research Achievements

In the present study, we demonsrated that the lack of Elovl6 has a causative role in lung pathology. Apoptosis and ROS production were increased in Elovl6－/－ lung. Alveolar type II epithelial cells isolated from Elovl6－/－ mice and LA-4 cells produced increased levels of ROS. Elovl6 deficiency increased PA and decreased OA and PUFA content in alveolar type II epithelial cells both in vivo and in vitro. Expressions of the genes for FADS1, FADS2, FATPs and FAT/CD36 were significantly reduced in Elovl6－/－ mice, suggesting that cellular uptake of long-chain FAs, including PUFA, was impaired in Elovl6－/－ mice.

Research Products

• [Journal Article] Glucose is preferentially utilized for biomass synthesis in pressure-overloaded hearts: Evidence from fatty acid binding protein-4 and -5 knockout mice. (2018)
  • Author(s): Umbarawan Y, Syamsunarno MRAA, Koitabashi N, Yamaguchi A, Hanaoka H, Hishiki T, Nagahata-Naito Y, Obinata H, Sano M, Sunaga H, Matsui H, Tsushima Y, Suematsu M, Kurabayashi M, Iso T
  • Journal Title: Cardiovascular Research Volume: - Pages: 1132-1144
  • DOI: 10.1093/cvr/cvy063
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Robust suppression of cardiac energy catabolism with marked accumulation of energy substrates during lipopolysaccharide-induced cardiac dysfunction in mice. (2017)
  • Author(s): Umbarawan Y, Syamsunarno MRAA, Obinata H, Yamaguchi A, Sunaga H, Matsui H, Hishiki T, Matsuura T, Koitabashi N, Obokata M, Hanaoka H, Haque A, Kunimoto F, Tsushima Y, Suematsu M, Kurabayashi M, Iso T.
  • Journal Title: Metabolism Volume: ７７ Pages: 47-57
  • Peer Reviewed / Open Access
• [Journal Article] Fibroblast growth factor 23 inhibits osteoblastic gene expression and induces osteoprotegerin in vascular smooth muscle cells. (2016)
  • Author(s): Nakahara T, Kawai-Kowase K, Matsui H, Sunaga H, Utsugi T, Iso T, Arai M, Tomono S, Kurabayashi M..
  • Journal Title: Atherosclerosis. Volume: 253 Pages: 102-110
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Elongation of Long-Chain Fatty Acid Family Member 6 (Elovl6)-Driven Fatty Acid Metabolism Regulates Vascular Smooth Muscle Cell Phenotype Through AMP-Activated Protein Kinase/Krupple-Like Factor 4 (AMPK/KLF4) Signaling. (2016)
  • Author(s): Sunaga H, Matsui H, Anjo S, Syamsunarno MR, Koitabashi N, Iso T, Matsuzaka T, Shimano H, Yokoyama T, Kurabayashi M
  • Journal Title: J Am Heart Assoc Volume: 5
  • DOI: 10.1161/jaha.116.004014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Elovl6-driven fatty acid metabolism regulates hypertrophic response in the heart subjected to pressure overload in mice. (2018)
  • Author(s): 須永浩章
  • Organizer: 第82回日本循環器学会
• [Presentation] A shift of energy substrate shift from fatty acids to glucose exacerbates cardiac dysfunction during pressure overload: A lesson learned from fatty acid binding protein-4 and -5 knockout mice (2017)
  • Author(s): Yogi Umbarawan
  • Organizer: 日本循環器学会
  • Place of Presentation: 金沢市
  • Year and Date: 2017-03-17