Prevention of NASH progression by improvement of intestinal mucosal barrier function using STAM mice

• Project/Area Number: 25860525
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Niigata University
• Principal Investigator: HONDA Yutaka 新潟大学, 医歯学総合病院, 医員 (20643547)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: NASH / タイトジャンクション / 腸粘膜バリアー / STAMマウス / 調粘膜バリアー

Outline of Final Research Achievements

Non-alcoholic steatohepatitis(NASH) is associated with diabetes, and progresses from fatty liver to steatohepatitis, liver fibrosis, and finaly to liver cirrhosis. It is also related to hepatocellular carcinoma(HCC). Recently, impaired mucosal barrier function is considered as an disease-progression factor for NASH.
We have developed a new animal model of NASH (STAM mouse), in which all the model mice show NASH, and progess to fibrosis, following development of multiple HCC later. Using this STAM mice, we analyzed expression level of several tight junction proteins in both colon and liver.Real time PCR analysis for both colon and liver showed the elevation of mRNA of Zo-1 in the phase of fatty liver, and decrease of mRNAs of claudin 1, occuludin, and connexin 43, in the NASH phase, suggesting that impaired mucosal barrier function might contribute to the progression of NASH from fatty liver to NASH, fibrosis, cirrhosis, and finally to HCC.

Research Products

• [Journal Article] A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma. (2013)
  • Author(s): Fujii M, Kenichi Watanabe et al.
  • Journal Title: Med Mol Morphol. Volume: in press Issue: 3 Pages: 141-152
  • DOI: 10.1007/s00795-013-0016-1
  • NAID: 10031203181
  • Peer Reviewed
• [Presentation] Endoscopic submucosal injection of a synthesized anti-CHST15 dsRNA for sulfated glycosaminoglycan is a safe and beneficial treatment for patients with Crohn’s disease who do not respond sufficiently to the conventional treatment. (2014)
  • Author(s): Suzuki K, Yokoyama J, Kawauchi Y, Honda Y, Asakura H, Okazaki K, Suzuki Y, Sameshima Y, Fukushima T, Fujii M, Hashiguchi T, Mizumoto S, Sugahara K, Yoneyama Hiroyuki.
  • Organizer: 2015 DDW, Chicago.
  • Place of Presentation: Chicago, IL, USA.
  • Year and Date: 2014-05-04
• [Book] Vimentin: Concepts and molecular mechanisms (2013)
  • Author(s): Suzuki K, Nagata M, Kawase T, Uematsu K, Honda Y, Kawauchi Y, Yokoyama J, Arumugam S, Thandavarayan RA, Yoneyama H, Watanabe K, Asakura H.
  • Total Pages: 170
  • Publisher: Nova Science Publishers, Inc.
• [Book] Mast cells. Phenotypic features, biological functions and role in immunity. (2013)
  • Author(s): Suzuki K, Nagata M, Kawase T, Uematsu K, Honda Y, Kawauchi Y, Yokoyama J, Arumugam S, Thandavarayan RA, Yoneyama H, Watanabe H, Asakura H.
  • Total Pages: 301
  • Publisher: Nova Science Publishers, Inc.