Abstract
Hepatic fibrosis is the consequence of an unresolved wound healing process in response to chronic liver injury and involves multiple cell types and molecular mechanisms. The hepatic endocannabinoid and apelin systems are two signalling pathways with a substantial role in the liver fibrosis pathophysiology—both are upregulated in patients with advanced liver disease. Endogenous cannabinoids are lipid-signalling molecules derived from arachidonic acid involved in the pathogenesis of cardiovascular dysfunction, portal hypertension, liver fibrosis, and other processes associated with hepatic disease through their interactions with the CB1 and CB2 receptors. Apelin is a peptide that participates in cardiovascular and renal functions, inflammation, angiogenesis, and hepatic fibrosis through its interaction with the APJ receptor. The endocannabinoid and apelin systems are two of the multiple cell-signalling pathways involved in the transformation of quiescent hepatic stellate cells into myofibroblast like cells, the main matrix-producing cells in liver fibrosis. The mechanisms underlying the control of hepatic stellate cell activity are coincident despite the marked dissimilarities between the endocannabinoid and apelin signalling pathways. This review discusses the current understanding of the molecular and cellular mechanisms by which the hepatic endocannabinoid and apelin systems play a significant role in the pathophysiology of liver fibrosis.
Highlights
Hepatic fibrosis is the excessive accumulation of connective tissue proteins, collagens, in the liver extracellular matrix [1]
This review focuses on recent advances in elucidating the roles of the endocannabinoid and apelin systems in liver fibrosis and their potential clinical relevance
Endopeptidases cleave the apelin prepropeptide into a 55 amino acid molecule, molecule, which in turn is fragmented by the angiotensin-converting enzyme 2 (ACE2) generating whichthe in following turn is fragmented by the angiotensin-converting enzyme theThis following bioactive isoforms: apelin 36, apelin 17, apelin
Summary
Hepatic fibrosis is the excessive accumulation of connective tissue proteins, collagens, in the liver extracellular matrix [1]. NAFLD is characterized by an abnormal accumulation of fatty acids into hepatocytes and includes a wide spectrum of liver diseases, ranging from mild to severe steatosis and non-alcoholic steatohepatitis (NASH) [3] Both NAFLD and NASH have the potential to evolve into liver fibrosis and cirrhosis. Most strategies aimed at interfering with liver fibrosis focus on the inhibition of HSC activation, the modulation of inflammatory response, or the reduction of hepatocyte damage by targeting and modulating multiple cell signalling pathways [4]. Two of these signalling pathways, which have significant impact on the pathophysiology of liver fibrosis, are the endocannabinoid and apelin systems. We emphasize recent findings regarding the cellular and molecular mechanisms by which these endogenous systems are involved in liver fibrosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
