Wound Healing Responses at the Gastrointestinal Epithelium: a Close Look at Novel Regulatory Factors and Investigative Approaches

Zusammenfassung

Eine einschichtige Lage von Epithelzellen kleidet den Gastrointestinaltrakt höherer Lebewesen aus und trennt verschiedenste Antigene im Lumen des Darmes von den Immunzellen des Wirtsorganismus in der Lamina propria. Störungen dieser epithelialen Barriere, wie sie beispielsweise im Rahmen von chronisch entzündlichen Darmerkrankungen, von Darmischämien oder infolge bakterieller Infektionen beobachtet werden, induzieren eine ausgeprägte Entzündungsreaktion, die – primär protektiv – überschießen und den Wirtsorganismus dann gefährden kann. Deshalb führen epitheliale Verletzungen zur raschen Induktion einer lokalen Wundheilungsantwort, deren Ziel es ist, die Kontinuität der Epitheldecke und damit die Barrierefunktion wiederherzustellen. Teil dieser Schutzmechanismen ist neben der Epithelzell-Proliferation auch die koordinierte Migration von Epithelzellen in das Wundgebiet bis zum Wundschluss. Zahlreiche Faktoren modulieren diese Prozesse. Sie werden von den Epithelzellen selbst, von Zellen der Lamina propria wie auch von Mikroorganismen im Darmlumen synthetisiert. Dieser Übersichtsartikel fasst die im Rahmen neu entwickelter Ansätze jüngst erweiterten Erkenntnisse zur zellulären Signaltransduktion und der auf sie einwirkenden Faktoren im Rahmen der gastrointestinalen epithelialen Wundheilung und Homeostase kurz zusammen.

Abstract

The gastrointestinal epithelium functions as an important physical barrier that separates the rich, diverse, and potentially immunogenic luminal content from the underlying mucosal immune system. In pathological situations such as inflammatory bowel disease, ischemic/hypoxic episodes and bacterial infection, insults to the intestinal epithelium threaten the integrity of the mucosal barrier and represent a huge challenge for the host. During episodes of epithelial injury and barrier breakdown, the host initiates a rapid wound healing response aimed at resealing the gap region and reestablishing homeostasis. This response named ”restitution” involves migration of epithelial cells toward the injured regions, as well as epithelial cell proliferation until the gap is closed and the barrier function is reestablished. These biological processes are influenced by a variety of factors derived from the gastrointestinal microenvironment, including host epithelial and lamina propria cells, as well as the microbiota, and the dietary and non-dietary components present in the gastrointestinal lumen. In this manuscript, we will review both host signaling events and luminal factors that influence the wound healing response and have an impact on host homeostasis.

gastrointestinale Epithelzellen - Wundheilung - Schutzmechanismen - Signaltransduktion

gastrointestinal epithelium - wound healing - microbial host interaction - cell signaling

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