Matrix metalloproteinases in intestinal fibrosis

Intestinal fibrosis is a common complication in patients suffering from inflammatory bowel disease (IBD), in particular Crohn's disease (CD). Unfortunately, intestinal fibrosis is not yet preventable, and cannot be treated by other interventions than surgical removal at this moment. Intestinal fibrosis is characterized by excessive accumulation of extracellular matrix (ECM), which is caused by activated fibroblasts and smooth muscle cells. Accumulation of ECM results from an imbalanced production and degradation of ECM. ECM degradation is mainly performed by matrix metalloproteinases (MMPs), enzymes that are counteracted by tissue inhibitors of MMPs (TIMPs). In IBD patients, MMP activity (together with other protease activities) is increased. At the same time, CD patients have a generally lower MMP activity compared to ulcerative colitis patients, who usually do not develop intestinal strictures or fibrosis. The exact regulation and role(s) of these MMPs in fibrosis are far from understood. Here, we review the current literature about ECM remodeling by MMPs in intestinal fibrosis and their potential role as biomarkers for disease progression or druggable targets.