Targeting Extracellular RNA Mitigates Hepatic Lipotoxicity and Liver Injury in NASH

Non-alcoholic steatohepatitis (NASH) is a clinically serious stage of non-alcoholic fatty liver disease (NAFLD). Histologically characterized by hepatocyte ballooning, immune cell infiltration, and fibrosis, NASH, at molecular level, involves lipid-induced death cytokine production. Currently, there are very few diagnostic biomarkers available to screen for no pharmacological intervention its treatment. In this study, we show that damage induced lipotoxicity results in the release extracellular RNAs (eRNAs), which serve as damage-associated patterns (DAMPs) stimulate expression pro-apoptotic pro-inflammatory cytokines, aggravate inflammation, lead HepG2 cells. Furthermore, inhibition eRNA activity RNase 1 significantly increases cellular viability reduces NF-kB-mediated Similarly, administration improves hepatic steatosis, inflammatory injury markers murine NASH model. Therefore, first time, underscores therapeutic potential inhibiting action novel strategy