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.

TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury

“…Interestingly, Smad3 -null mice showed lowered serum ALP activity (a cholangiocyte injury marker) associated with acute liver injury compared with wild-type mice, but they did not have altered serum ALT activity (a hepatocyte injury marker). In chronic liver disease, such as cholestasis and primary biliary cirrhosis, chronic autoimmune-mediated damage to bile duct epithelial cell (BDEC) can cause infl ammation with activation of wound healing in the liver ( 39 ). In bile duct ligation (BDL) model of obstructive cholestasis, the BDEC-expressed ␤ 6 integrin activates the latent TGF ␤ ( 40, 41 ).…”

Bone Morphogenetic Proteins and Signaling Pathway in Inflammatory Bowel Disease

“…It occurs as a result of different types of chronic inflammation, initiated in various cellular sources, but all result in deregulation of extracellular matrix turnover (Burke 2007, Fiocchi & Lund, 2011. TGFβ is described as the most potent profibrotic factor of several (a) PCNA staining (b) Naphtol AS-D chloroacetate esterase staining Fig.…”

Induction of chronic pancreatitis by pancreatic duct ligation activates BMP2, apelin, and PTHrP expression in mice

“…Although utilization of experimental models has helped identify molecular mechanisms linked to development of CP (19,32,41,47), significant gaps persist in our knowledge of endogenous factors that function to either inhibit or amplify the inflammatory-fibrosis cascade (7,9,41), a key component of the CP disease process.…”