Maintenance of intestinal barrier function by focal adhesion kinase

• Project/Area Number: 25460378
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Asahikawa Medical College
• Principal Investigator: TANIGUCHI Takanobu 旭川医科大学, 医学部, 教授 (60217130)
• Co-Investigator(Kenkyū-buntansha): YAZAWA Takashi 旭川医科大学, 医学部, 講師 (00334813) ; TAKEUCHI Masayuki 旭川医科大学, 医学部, 助教 (40226999) ; KATOH Tsuyoshi 旭川医科大学, 医学部, 准教授 (60194833) ; UWADA Junsuke 旭川医科大学, 医学部, 助教 (70580314)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: focal adhesion kinase / intestinal barrier / muscarinic cholinoceptor / 炎症性腸疾患 / 上皮バリア / focal adhesion kinase / MAP kinase / ムスカリン受容体 / acetylchoine / acetylcholine

Outline of Final Research Achievements

Tumor necrosis factor alpha (TNF) induced the reduction of TER in HT-29/B6 monolayers which was attenuated by acetylcholine or charbacol treatment. This attenuation was cancelled by the addition of atropine. TNF-induced activation of NF-kB system was inhibited by acetylcholine or charbacol treatment. This inhibition was also suppressed by the addition of atropine. TNF induced increase in the expression of inflammatory genes such as COX-2 and IL-8 genes and the excretion of IL-8 in the culture medium which were attenuated by charbacol treatment. This attenuation was also cancelled by the addition of atropine.
These results suggest that muscarinic signaling system may enforce intestinal epithelial barrier function against inflammatory barrier disruption and may prevent inflammatory expansion at the same time.

Research Products

• [Journal Article] Activation of focal adhesion kinase via M1 muscarinic acetylcholine receptor is required in restitution of intestinal barrier function after epithelial injury. (2015)
  • Author(s): Khan RI, Yazawa T, Anisuzzaman AS, Semba S, Ma Y, Uwada J, Hayashi H, Suzuki Y, Ikeuchi H, Uchino M, Maemoto A, Muramatsu I, Taniguchi T.
  • Journal Title: Biochim Biophys Acta Volume: 1842 Pages: 635-645
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Differentiation of mesenchymal stem cells into gonad and adrenal steroidogenic cells. (2015)
  • Author(s): Yazawa T, Imamichi Y, Miyamoto K, Umezawa A, Taniguchi T.
  • Journal Title: World J Stem Cells Volume: 6 Pages: 203-212
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Activation of focal adhesion kinase via M1 muscarinic acetylcholine receptor is required in restitution of intestinal barrier function after epithelial injury (2014)
  • Author(s): Md Rafiqul Islam Khan, Takashi Yazawa, Abu Syed Md Anisuzzaman, Shingo Semba, Yanju Ma, Junsuke Uwada, Hisayoshi Hayashi, Yuichi Suzuki, Hiroki Ikeuchi, Motoi Uchino, Atsuo Maemoto, Ikunobu Muramatsu, Takanobu Taniguchi
  • Journal Title: BBA Molecular Basis of Disease Volume: 1842 Issue: 4 Pages: 635-645
  • DOI: 10.1016/j.bbadis.2013.12.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] M1 ia a major subtype of muscarinic acetylcholine receptors on mouse colonic epitjelial cells (2013)
  • Author(s): Khan MR, Anisuzzaman AS, Semba S, Ma Y, Uwada J, Hayashi H, Suzuki Y, Takano T, Ikeuti H, Uchino M, Ushikubi F, Muramatsu I, Taniguchi T
  • Journal Title: J Gastroenterol Volume: in press Issue: 8 Pages: 885-896
  • DOI: 10.1007/s00535-012-0718-5
  • Peer Reviewed
• [Presentation] Activation of FAK via M1 muscarinic acetylcholine receptor is required in restitution of intestinal barrier function after epithelial injury. (2015)
  • Author(s): Islam T, Khan MRI, Yazawa T, Taniguchi T.
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2015-10-16
• [Presentation] Activation of FAK via M1 muscarinic acetylcholine receptor is required in restitution of intestinal barrier function after epithelial injury (2014)
  • Author(s): イスラム タリクル, カーン ロフィクルイスラム, 矢澤 隆志, 谷口 隆信
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-10-16
• [Presentation] ムスカリンＭ１受容体を介したFAKの活性化による腸上皮バリア機能の維持と修復
  • Author(s): 矢澤 隆志
  • Organizer: 第８６回日本生化学学会大会
  • Place of Presentation: パシフィコ横浜（神奈川県）