Involvement of the transcription factor HIF-1 in the cell-to-cell adhesion system

• Project/Area Number: 25462457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Kansai Medical University
• Principal Investigator: NISHI Kenichiro 関西医科大学, 医学部, 講師 (50340716)
• Co-Investigator(Kenkyū-buntansha): HIROTA Kiichi 関西医科大学, 医学部, 准教授 (00283606)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 周術期管理 / 低酸素 / 炎症 / HIF-1 / 細胞間バリア / タイトジャンクション / 接着分子 / 酸素代謝

Outline of Final Research Achievements

The respiratory epithelium forms an important barrier against inhaled pollutants and microorganisms, and its barrier function is often compromised during hypoxic insults. Epithelial activation of hypoxia- inducible factor-1 (HIF-1) represents one feature of airway inflammation, but the functional importance of HIF-1 within the respiratory epithelium is largely unknown. We evaluated the impact of HIF-1 activation on loss of epithelial barrier function during hypoxic insults.
Using several types of cell lines, we confirmed that expression of various adhesion molecules were modulated under hypoxic conditions in an HIF-1-dependent manner and that a critical involvement of HIF-1 in dysregulation of epithelial barrier function during hypoxic and inflammatory insults.

Research Products

• [Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha (2015)
  • Author(s): Goto Y, Zeng L, YeomCJ, Zhu Y, Morinibu A, Shinoyam K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H.
  • Journal Title: Nature communication Volume: 6 Pages: 1-10
  • DOI: 10.1038/ncomms7153
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of hypozia-inducible factors in the dysregulation of oxygen homeostasis in sepsis (2015)
  • Author(s): Hirota K.
  • Journal Title: Cardiovascular & hematological disorders drug targets. Volume: 15 Pages: 29-40
  • DOI: 10.2174/1871529x15666150108115553
  • Peer Reviewed / Open Access
• [Journal Article] The volatile anesthetic isoflurane differentially suppresses the induction of erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice in an hypoxia-inducible factor-2-dependent manner. (2014)
  • Author(s): Kai S, Tanaka T, Matsuyama T, Suzuki K, Hirota K.
  • Journal Title: Eur J Pharmacol Volume: 732C Pages: 43-49
  • DOI: 10.1016/j.ejphar.2014.03.020
  • Peer Reviewed
• [Journal Article] Differential roles of prostaglandin E-type receptors in activation of hypoxia-inducible factor 1 by prostaglandin E1 in vascular-derived cells under non-hypoxic conditions. (2013)
  • Author(s): Suzuki K, Nishi K, Takabuchi S, Kai S, Matsuyama T, Kurosawa S, Adachi T, Maruyama T, Fukuda K, Hirota K.
  • Journal Title: Peer J Volume: 1 Pages: 1-20
  • DOI: 10.7717/peerj.220
  • Peer Reviewed
• [Journal Article] 疾患の病態生理学と低酸素誘導性因子 (2013)
  • Author(s): 広田喜一
  • Journal Title: 細胞 Volume: 45 Pages: 415-418