miR-141-3p-loaded extracellular vesicles ameliorate intrahepatic bile duct stone disease by decreasing MUC5AC expression via the MAPK pathway.

Abstract

Intrahepatic bile duct stone disease has a high morbidity in China, with a high rate of additional surgery, a high rate of cancer development, and a high disease burden. Activation of the MAPK pathway leading to up-regulation of MUC5AC expression is an important factor in the formation of intrahepatic bile duct stones. Exosomes or extracellular vesicles (EVs) can be used as therapeutic vectors to encapsulate and carry drugs into diseased cells to achieve a therapeutic effect. The current study alleviated intrahepatic bile duct stone disease by preparing EVs carrying miR-141-3p. First, the researchers loaded mesenchymal stem cell (ESC)-derived EVs with miR-141-3p (miR-141-3p-EVs) and verified the phenotypes and characteristics of miR-141-3p-EVs. miR-141- 3p-EVs successfully reduced the inflammatory level of human biliary epithelial cells (HIBEC) and lowered, via the MAPK pathway, MUC5AC expression. In an experiment involving an animal model of intrahepatic bile duct stones, miR-141-3p-EVs effectively alleviated stone formation, and the intrinsic mechanism was associated with the decreased level of MAPK pathway expression. In conclusion, results suggested that the EV-based strategy of miR- 141-3p delivery to intrahepatic bile duct epithelial cells has value and provides a new approach for the treatment of intrahepatic biliary stone disease.