Intestinal Fibrosis and Liver Fibrosis: Consequences of Chronic Inflammation or Independent Pathophysiology?

Abstract

Background: Intestinal fibrosis and liver fibrosis represent a significant burden for our patients and health-care systems. Despite the severe clinical problem and the observation that fibrosis is reversible, no specific antifibrotic therapies exist.

Summary: In this review, using an 'East-West' scientific collaboration, we summarize the current knowledge on principal mechanisms shared by intestinal fibrosis and liver fibrosis. We furthermore discuss inflammation as the cause of fibrogenesis in both entities, depict unique features of intestinal and hepatic fibrosis, and provide a future outlook on the development of antifibrotic therapies.

Key messages: A collaborative effort in the field of fibrosis, covering multiple organ systems, will have the highest chance of leading to the development of a successful antifibrotic intervention.

Keywords: Extracellular matrix; Inflammatory bowel disease; Liver cirrhosis; Organ fibrosis.

Fig. 1

Distribution of vitamin A-storing stellate cells in the lamprey. In the lamprey, vitamin A-storing cells represent the visceral type of fibroblasts that are present uniformly in the organs of splanchnic and intermediate mesodermal origin. These are distinguishable from the cells of somatic mesodermal origin such as dermal fibroblasts. Especially, abundant vitamin A-storing cells are found in the lamina propria of the gastrointestinal mucosa in the lamprey. Reproduced with permission from Wold et al. [11].

Fig. 2

TGF-β/Smad signal and its antagonists in organ fibrosis. TGF-β and its intracellular mediators, the Smad proteins, are the most potent accelerators of collagen production in the liver and intestine. TGF-β not only promotes collagen production but also activates HSCs and myofibroblasts and suppresses MMP expression, leading to the progression of liver and intestinal fibrosis. Among the Smad/BMP superfamily members, Smad 3 plays a pivotal role in stimulating collagen gene transcription, while Smad 7 inhibits the TGF-β signal by suppressing the phosphorylation and the subsequent nuclear translocation of Smad 3. BMP7 and hepatocyte growth factor (HGF) have been reported to suppress organ fibrosis by counteracting TGF-β action on the type I collagen gene.