Fibrin-mediated integrin signaling plays a critical role in hepatic regeneration after partial hepatectomy in mice
Journal Title: Annals of Hepatology - Year 2016, Vol 15, Issue 5
Abstract
Background. The regenerative capacity of the liver is critical for proper responses to injury. Fibrin extracellular matrix (ECM) deposition is a common response to insult and contributes to inflammatory liver injury. However, the role of this matrix in hepatic regeneration has not been determined. Objective. The purpose of this study was first to determine the role of fibrin ECM in hepatic regeneration followed by the role of the fibrin-binding αvβ3 integrin in mediating this effect. Material and methods. C57Bl/6J (WT) or PAI-1 knockout (KO) mice underwent 70% partial hepatectomy (PHx); plasma and histologic indices of regeneration were determined, as well as expression of key genes involved in hepatic regeneration. Results. PHx promoted transient fibrin deposition by activating coagulation and concomitantly decreasing fibrinolysis. Inhibiting fibrin deposition, either by blocking thrombin (hirudin) in WT mice or by knocking out PAI-1, was associated with a decrease in hepatocyte proliferation after PHx. This strongly suggested a role for fibrin ECM in liver regeneration. To investigate if αvβ3 integrin mediates this action, we tested the effects of the anti-αvβ3 cyclic peptide RGDfV in animals after PHx. As was observed with inhibition of fibrin deposition, competitive inhibition of αvβ3 integrin delayed regeneration after PHx, while not affecting fibrin deposition. These effects of RGDfV correlated with impaired angiogénesis and STAT3 signaling, as well as transient endothelial dysfunction. In conclusion, these data suggest that αvβ3 integrin plays an important role in coordinating hepatocyte division during liver regeneration after PHx via crosstalk with fibrin ECM.
Authors and Affiliations
Juliane Beier, Luping Guo, Jeffrey Ritzenthaler, Swati Joshi-Barve, Jesse Roman, Gavin Arteel
Keywords
Related Articles
- EP ID EP78622
- DOI 10.5604/16652681.1212587
- Views 142
- Downloads 0
Smoking as a risk factor for autoimmune liver disease: what we can learn from primary biliary cirrhosis
Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating an...
Minimally invasive treatment of Mirizzi’s syndrome: is there a safe way? Report of a case series
Mirizzi’s syndrome (MS) is a rare complication of the inveterate biliary lithiasis. Diagnostic and therapeutic standardization is still missing, especially since laparoscopic cholecystectomy has become the gold standard...
Nonvariceal upper gastrointestinal bleeding in patients with liver cirrhosis. Clinical features, outcomes and predictors of in-hospital mortality. A prospective study
Background. Clinical and endoscopic features of cirrhotic patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) have been rarely reported and clinical outcomes and predictors of mortality have not been evalu...
Predicting portal hypertension and variceal bleeding using non-invasive measurements of metabolic variables
Background & aim. This study assessed the involvement of metabolic factors (anthropometric indices, insulin resistance (IR) and adipocytokines) in the prediction of portal hypertension, esophageal varices and...
Comparison of Dynamic Changes Among Various Prognostic Scores in Viral Hepatitis-Related Acute Liver Failure
Introduction and aim. Multiple prognostic scores are available for acute liver failure (ALF). Our objective was to compare the dynamicity of model for end stage liver disease (MELD), MELD-sodium, acute liver failure earl...