LncRNA 220, a newly discovered long non-conding RNA mediating apoptosis and autophagy in Kupffer cells in LPS-induced endotoxemic mice through the XBP1u-PI3K-AKT-mTOR pathway.

Abstract

Abstract Sepsis, recognized as an acute systemic inflammatory syndrome, possesses the capacity to induce damage to multiple organs, potentially leading to organ failure. Acute liver injury (ALI) is an inflammatory results of immune response disorder associated-with sepsis. Multiple studies have demonstrated that long non-coding RNAs (lncRNAs) exert regulatory influence over the advancement of various diseases, although their specific regulatory mechanisms remain largely unknown. Here, a novel lncRNA, designated as 220, was identified through high-throughput sequencing, with extremely differential expression in the livers of LPS-induced endotoxemic mice during the period of 8 h. Moreover, in LPS-treated Kupffer cells, 220 participated in the down-regulation on the apoptotic and the autophagic processes through the PI3K-AKT-mTOR pathway by stabilizing X-box protein 1 u (Xbp1u) mRNA and mediating its translation in endoplasmic reticulum stress (ERS), thus ultimately modulate the process of LPS-associated ALI. Furthermore, the verification of our discoveries through clinical databases further indicated that both 220 and XBP1 were integral components in the diagnostic and therapeutic procedures of advanced sepsis. Our study establishes 220 as a novel regulator participating in autophagic and apoptotic mechanisms within LPS-treated Kupffer cells. Moreover, 220 could be regarded as a possible molecular objective with clinical importance in severe septic conditions.