Matrix metalloproteinase MMP9 maintains epithelial barrier function and preserves mucosal lining in colitis associated cancer

作者：Adani Pujada, Lewins Walter, Aashka Patel, Tien Anh Bui, Zhan Zhang, Yuchen Zhang, Timothy L. Denning, Pallavi Garg · 发表于：Oncotarget · 年份：2017 · DOI：10.18632/oncotarget.21841 · 被引用次数：62 · 研究领域：Inflammatory Bowel Disease、Anorectal Disease Treatments and Outcomes、Inflammatory Biomarkers in Disease Prognosis

// Adani Pujada 1 , Lewins Walter 1 , Aashka Patel 2 , Tien Anh Bui 2 , Zhan Zhang 1 , Yuchen Zhang 1 , Timothy Luke Denning 1 and Pallavi Garg 1 1 Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA 2 Department of Biology, Georgia State University, Atlanta, GA, USA Correspondence to: Pallavi Garg, email: pgarg@gsu.edu Keywords: colitis associated cancer; microbiota; MMP9; IL-22; A. muciniphila Received: April 19, 2017     Accepted: August 14, 2017     Published: October 17, 2017 ABSTRACT In colitis associated cancer (CAC), chronic inflammation exposes the epithelial mucosal defensive lining to inflammatory mediators such as cytokines and anti-microbial peptides (AMPs) causing the dysbiosis of microbiota population and the dysregulation of immune response. Matrix Metalloproteinases (MMPs) are zinc dependent endopeptidases which mediate inflammation, tissue remodeling, and carcinogenesis. MMP9 is undetectable in healthy tissue, although highly upregulated during inflammation and cancer. We have previously shown that MMP9 plays a protective role in CAC opposite to its conventional role of acute inflammation and cancer mediator. In this study, we investigated the mechanistic role of MMP9 in preserving the epithelial mucosal integrity to suppress the progression of tumor microenvironment in CAC. We used transgenic mice constitutively expressing MMP9 in colonic epithelium (TgM9) as an in vivo model and intestinal c...