The effect of SLCO2A1 loss-of-function mutations in the SLCO2A1 gene and the secretion of PGE2 in intestinal homeostasis

• Project/Area Number: 17H07022
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Osaka City University
• Principal Investigator: Nishida Yu 大阪市立大学, 大学院医学研究科, 後期臨床研究医 (60804705)
• Research Collaborator: Hosomi Shuhei ; Nakata Rieko ; Nakanishi Takeo ; Nakamura yoshinobu
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: SLCO2A1 / 非特異性多発性小腸潰瘍症

Outline of Final Research Achievements

We used systemic knockout mice (SLCO2A1-/-) and conditional SLCO2A1 knockout mice in intestinal epithelium (SLCO2A1ΔIEC). SLCO2A1-/- mice had no spontaneous enteritis or colitis. In DSS colitis model, SLCO2A1-/- mice had more severe colitis compared with wild-type mice, but not SLCO2A1ΔIEC mice. These findings suggest that the second hit is necessary for the onset of ulceration and SLCO2A1 are important for intestinal homeostasis. SLCO2A1 in cells other than intestinal epithelium is important for inflammation control and tissue repair. Our findings might have potential therapeutic implications for intestinal inflammation associated with SLCO2A1.

Academic Significance and Societal Importance of the Research Achievements

非特異性多発性小腸潰瘍症の疾患遺伝子として、プロスタグランジン輸送蛋白であるSLCO2A1の変異が報告され、その発現・機能の低下が病因であると推定されている。しかし、SLCO2A1機能低下による腸炎発症メカニズムは未だ明らかとなっておらず有効な治療法も確立されていない。今回の検討により、SLCO2A1における潰瘍発症機序の一端が判明した。今後、非特異性小腸潰瘍症の病態や治療薬の創薬につながることが期待される。

Research Products

• [Presentation] SLCO2A1 DEFICIENCY EXACERBATES EXPERIMENTAL COLITIS VIA INFLAMMASOME ACTIVATION IN MACROPHAGES (2019)
  • Author(s): Rieko Nakata, Shuhei Hosomi, Yoshinobu Nakamura, Naoko Sugita, Yu Nishida, Shigehiro Itani, Koji Otani, Fumio Tanaka, Yasuaki Nagami, Noriko Kamata, Koichi Taira, Hirokazu Yamagami, Tetsuya Tanigawa, Toshio Watanabe, Takeo Nakanishi, Ikumi Tamai, Yasuhiro Fujiwara
  • Organizer: Digestive Disease Week
  • Int'l Joint Research
• [Presentation] 腸管粘膜傷害におけるプロスタグランジン輸送蛋白(Slco2a1)の役割の検討 (2018)
  • Author(s): 中田理恵子、細見周平、奥田博朗、古瀬昧澄、杉田奈央子、西田裕、鋳谷成弘、鎌田紀子、山上博一、谷川徹也、渡辺俊雄、中村吉伸、中西猛夫、藤原靖弘
  • Organizer: 日本消化器免疫学会