Themes in fibrosis and gastrointestinal inflammation

Abstract

Wound healing is an appropriate response to inflammation and tissue injury in the gastrointestinal tract. If wound healing responses are excessive, perpetuated, or prolonged, they lead to fibrosis, distortion of tissue architecture, and loss of function. This introductory editorial and the minireviews or reviews in this themes series highlight the diversity in severity and location of fibrosis in response to gastrointestinal inflammation. The multiplicity of cellular and molecular mediators and new players, including stem cells or extracellular matrix-producing cells derived from nonmesenchymal cell types, is reviewed. Comparisons of inflammation-induced fibrosis across organ systems and the need for integrated and systems-based molecular approaches, new imaging modalities, well-characterized animal models, cell culture models, and improved diagnostic or predictive markers are reviewed. To date, intestinal fibrosis has received much less attention than inflammation in terms of defining mechanisms and underlying causes. This themes series aims to illustrate the importance of research in this area in gastrointestinal health and disease.

Fig. 1.

Hypothesized models of the link between different types of inflammation and regenerative, wound healing, or fibrotic responses. Left: regeneration and restoration of tissue architecture occur after superficial inflammation of limited duration such as uncomplicated gastroduodenal peptic ulcers or acute injury or loss of stable tissue such as intestinal muscle layers. Right: fibrosis occurs when regeneration and repair fail to restore normal tissue architecture. Discrete circumscribed scars form after localized but recurrent inflammation as occurs with repeated bouts of acute diverticulitis. Extensive scar tissue and fibrosis can permeate the entire tissue when the intestine is subject to chronic inflammation, as in inflammatory bowel disease, and tissue is constantly attempting wound repair. GI, gastrointestinal.