The intestinal tissue homeostasis – the role of extracellular matrix remodeling in inflammatory bowel disease

ABSTRACT

Introduction: Extracellular matrix (ECM) remodeling of the intestinal tissue is important in inflammatory bowel disease (IBD) due to the extensive mucosal remodeling. There are still gaps in our knowledge as to how ECM remodeling is related to intestinal epithelium homeostasis and healing of the intestinal mucosa.

Areas covered: The aim of this review is to highlight the importance of the ECM in relation to the pathogenesis of IBD, while addressing basement membrane and interstitial matrix remodeling, and the processes of wound healing of the intestinal tissue in IBD.

Expert opinion: In IBD, basement membrane remodeling may reflect the integrity of the intestinal epithelial-cell homeostasis. The interstitial matrix remodeling is associated with deep inflammation such as the transmural inflammation as seen in fistulas and intestinal fibrosis leading to fibrostenotic strictures, in patients with CD. The interplay between wound healing processes and ECM remodeling also affects the tissue homeostasis in IBD. The interstitial matrix, produced by fibroblasts, holds a very different biology as compared to the epithelial basement membrane in IBD. In combination with integration of wound healing, quantifying the interplay between damage and repair to these sub compartments may provide essential information in IBD patient profiling, mucosal healing and disease management.

KEYWORDS:

• Inflammatory bowel disease
• extracellular matrix
• mucosal healing
• inflammation
• fibrosis
• basement membrane
• interstitial matrix
• ECM remodeling
• serological biomarkers

Article highlights

• Extracellular matrix (ECM) remodeling (in which old ECM proteins, including collagens, laminins, elastin and proteoglycans are being degraded by proteases and replaced by newly synthesized ECM proteins) is an essential process in tissue homeostasis. Excessive ECM remodeling in IBD is driven by chronic intestinal inflammation, which leads to increased levels of degradation and may result in inadequate intestinal tissue healing, which eventually may cause excessive ECM formation and tissue deposition resulting in intestinal fibrogenesis.

• By evaluating ECM remodeling in IBD, crucial information about the state of the tissue may be obtained. This can be done by investigating ECM remodeling of the basement membrane and interstitial matrix in IBD.

• Increased protease activity is present in IBD patients. The proteases will be degraded in the intestinal tissue, leading to increased release of ECM protein fragments into the local tissue and into the circulation.

• A precise and quick work up for IBD patients is pivotal for optimal treatment strategies and to prevent future disease complications. Therefore, quantification of ECM remodeling in IBD patients may be utilized as surrogate markers for predicting intestinal fibrosis and fistula development as well as surrogate markers for intestinal mucosal healing.

Declaration of interest

This paper was not funded. The authors of this review declare that they have no conflict of interest.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.