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

2014 Fiscal Year Final Research Report

• 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
• Keywords: NASH / タイトジャンクション / 腸粘膜バリアー / STAMマウス

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.

Free Research Field

消化器内科学