Extracellular vesicles in metabolic dysfunction associated fatty liver disease: mechanisms, diagnostic and therapeutic implications

Abstract

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is increasing rapidly worldwide due to the obesity epidemic. Advanced stages of the MAFLD, such as non-alcoholic steatohepatitis (NASH) with advanced fibrosis or cirrhosis are affecting global health. Extracellular vesicles (EVs) are released by all cell types and are important in cell-to-cell communication and maintaining homeostasis, but they also play a role in the pathogenesis of various diseases. EVs contain biological information such as lipids, proteins, messenger RNAs (mRNAs), small RNAs, and DNA, and they act on (distant) target cells. The cargo of EVs is dependent on the type and the state of the releasing cell. EVs have been proposed as biomarkers, prognostic, and even therapeutic agents, also in the context of liver diseases. This review aims to give an overview of the current knowledge on EVs in MAFLD, including the role and interaction of EVs with different cell types in the liver. Several aspects of EVs, including their origin, characteristics, cargo, and functions are reviewed. Moreover, the potential of EVs as targets for the treatment of MAFLD is discussed.

Extracellular vesicles originating from steatotic hepatocytes promote hepatic stellate cell senescence via AKT/mTOR signaling

“…10 Recently, we reviewed the literature on the role of EVs in cell to cell communication in the context of MASLD. 11 Several studies investigated the content of EVs and demonstrated the presence of bioactive proteins as well as various RNA species (mRNA, miRNA), also in the context of MASLD. 12 miRNAs have the capacity to modulate various aspects of cellular function.…”

“…Their remarkable stability positions them as promising biomarkers with potential applications in disease diagnosis and prognosis. 11,13 Senescence is a state of (almost) irreversible cell cycle arrest. Induction of senescence in stellate cells has been proposed as a potential intervention to prevent and/ or reverse activation of HSCs and we have observed a reciprocal relation between the expression of activation markers and senescence markers in HSCs.…”

“…miRNAs have the capacity to modulate various aspects of cellular function. Their remarkable stability positions them as promising biomarkers with potential applications in disease diagnosis and prognosis 11,13 . Senescence is a state of (almost) irreversible cell cycle arrest.…”

“…In MASLD, EVs can be released by damaged and/or steatotic hepatocytes and these EVs can directly act on HSCs or indirectly on HSCs via Kupffer cells to promote inflammation and fibrogenesis 10 . Recently, we reviewed the literature on the role of EVs in cell to cell communication in the context of MASLD 11 . Several studies investigated the content of EVs and demonstrated the presence of bioactive proteins as well as various RNA species (mRNA, miRNA), also in the context of MASLD 12 .…”

Extracellular vesicles originating from steatotic hepatocytes promote hepatic stellate cell senescence via AKT/mTOR signaling

“…miRNAs have the capacity to modulate various aspects of cellular function. Their remarkable stability positions them as promising biomarkers with potential applications in disease diagnosis and prognosis 11,13 . Senescence is a state of (almost) irreversible cell cycle arrest.…”