The protective effect of lncRNA NEAT1/miR-122-5p/Wnt1 axis on hippocampal damage in hepatic ischemic reperfusion young mice

pubmed: wnt1 2023-06-01

Cell Signal. 2023 Jul;107:110668. doi: 10.1016/j.cellsig.2023.110668. Epub 2023 Mar 31.


Hepatic ischemic reperfusion (HIR) is a common pathophysiological process in many surgical procedures such as liver transplantation (LT) and hepatectomy. And it is also an important factor leading to perioperative distant organ damage. Children undergoing major liver surgery are more susceptible to various pathophysiological processes, including HIR, since their brains are still developing and the physiological functions are still incomplete, which can lead to brain damage and postoperative cognitive impairment, thus seriously affecting the long-term prognosis of the children. However, the present treatments of mitigating HIR-induced hippocampal damage are not proven to be effective. The important role of microRNAs (miRNAs) in the pathophysiological processes of many diseases and in the normal development of the body has been confirmed in several studies. The current study explored the role of miR-122-5p in HIR-induced hippocampal damage progression. HIR-induced hippocampal damage mouse model was induced by clamping the left and middle lobe vessels of the liver of young mice for 1 h, removing the vessel clamps and re-perfusing them for 6 h. The changes in the level of miR-122-5p in the hippocampal tissues were measured, and its influences on the activity as well as apoptotic rate of neuronal cells were investigated. Short interfering RNA modified with 2'-O-methoxy substitution targeting long-stranded non-coding RNA (lncRNA) nuclear enriched transcript 1 (NEAT1) as well as miR-122-5p antagomir were used to further clarify the role played by the corresponding molecules in hippocampal injury in young mice with HIR. The result obtained in our study was that the expression of miR-122-5p in the hippocampal tissue of young mice receiving HIR is reduced. Upregulated expression of miR-122-5p reduces the viability of neuronal cells and promotes the development of apoptosis, thereby aggravating the damage of hippocampal tissue in HIR young mice. Additionally, in the hippocampal tissue of young mice receiving HIR, lncRNA NEAT1 exerts some anti-apoptotic effects by binding to miR-122-5p, promoting the expression of Wnt1 pathway. An essential observation of this study was the binding of lncRNA NEAT1 to miR-122-5p, which upregulates Wnt1 and inhibits HIR-induced hippocampal damage in young mice.

PMID:37004832 | DOI:10.1016/j.cellsig.2023.110668