Hepatocyte-Derived Apoptotic Bodies as Pathological Intercellular Messengers in the Liver

Hepatocyte apoptotic bodies (ApopBDs) are extracellular vesicles formed during hepatocyte apoptosis. Although they were initially recognized as cellular waste and vesicles that clear toxic substances and viral infections in the liver, they are now known to serve as key mediators of intercellular communication that influence key metabolic and immune responses, such as inflammation, regeneration, and fibrosis. While numerous functions of ApopBDs in the liver are emerging, this review will focus on discussing their biogenesis, characterization, and roles in different liver diseases, with an emphasis on intercellular communication with liver-resident cells. The mechanisms of liver injury are convoluted by series of injurious crosstalk between hepatocyte ApopBDs and surviving resident cells. A unique feature of liver injury is a constant cycle of hepatocyte apoptosis, which has been attributed to crosstalk between surviving hepatocytes and their ApopBDs. The progression of liver injury is also affected by the activation of proinflammatory and profibrotic pathways such as TLR9/NLRP3 and JAK-STAT3. Given the expression of hepatocyte-specific molecular signatures on these ApopBDs, their application as diagnostic tools may improve the treatment of liver diseases. Although the science of hepatocyte ApopBDs is fairly recent and still emerging, in-depth understanding of this aspect of liver biology may provide a novel therapeutic option for the progression of liver damage.