Mechanisms and Models for Intestinal Fibrosis in IBD

Abstract

Intestinal fibrosis is a common outcome in IBD leading to significant morbidity that, to date, has no effective medical treatment. Current knowledge regarding potential mechanism(s) of intestinal fibrogenesis and stricture formation is limited, due in large part to the lack of relevant animal models. Although conventional models possess aspects that are advantageous to study specific mechanisms involved in gut fibrosis, most lack the features of a spontaneously occurring process leading to the formation of intestinal fibrotic lesions following mucosal inflammatory events and the ability to investigate the natural course of disease over time. This review aims to discuss established and novel animal models of gut fibrosis, particularly focusing on the advantages and disadvantages of each model system and the insights they bring to our understanding of the mechanisms of fibrogenesis. In fact, recent enhancements to existing models and the expansion of novel animal models of gut fibrosis is opening up multiple avenues for investigation which should stimulate progress in our mechanistic understanding of intestinal fibrogenesis and facilitate the development of effective pharmacotherapy in an area of significant unmet need.

Animal models for studying epithelial barriers in neonatal necrotizing enterocolitis, inflammatory bowel disease and colorectal cancer

“…Long-term administration of low dose TNBS results in chronic colitis that resembles human CD. 102 It has been reported that TNBS-induced mouse colitis share the similar pathogenesis involving NOD2, a key CD susceptibility gene. 103 Claudin-18 upregulation occurs in intestinal epithelia of both IBD patients and TNBS-treated mice 94 as does occludin 104 and ZO-1, ¡2, ¡3 downregulation.…”

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

“…The fibrotic development is closely associated with a cascade of processes, including epithelial cells injury and reconstitution, activation of immune cells and mesenchymal cells, as well as angiogenesis and lymphangiogenesis 11 . Moreover, increased deposition of ECM is mainly derived from abnormal activation of fibroblasts, myofibroblasts, and smooth muscle cells in response to gut inflammatory mediators 12 .…”

Expression of decorin in intestinal tissues of mice with inflammatory bowel disease and its correlation with autophagy

“…IBD usually occurs in young adults and is closely associated with inheritance, infection and immune function (3). IBD is harmful to health with characteristics including a high recurrence rate, high canceration rate and poor prognosis (4,5). Further investigation of the molecular mechanisms of IBD may provide valuable information for the treatment of IBD.…”