{Reference Type}: Journal Article
{Title}: Hypomethylated leptin receptor reduces cerebral ischaemia-reperfusion injury by activating the JAK2/STAT3 signalling pathway.
{Author}: Wang X;Wang Z;Liu S;Feng Y;Zhang T;Wu Z;Huang J;Zhao W;
{Journal}: J Int Med Res
{Volume}: 52
{Issue}: 8
{Year}: 2024 Aug
{Factor}: 1.573
{DOI}: 10.1177/03000605241261912
{Abstract}: <B>OBJECTIVE: </B>To investigate the cerebroprotective effects of leptin in vitro and in vivo via the Janus kinase-2 (JAK2)/transcription factor signal transducer and activators of transcription-3 (STAT3) pathway and leptin receptors (LEPR).<BR><B>METHODS: </B>The study used the cellular oxygen-glucose deprivation (OGD) model in PC12 cells and the middle cerebral artery occlusion (MCAO) rat model of cerebral ischaemia-reperfusion injury (CIRI) to assess changes in gene expression and protein levels following leptin pretreatment. The methylated DNA immunoprecipitation (MeDIP) assay measured DNA methylation levels.<BR><B>RESULTS: </B>The optimal leptin concentration for exerting neuroprotective effects against ischaemia-reperfusion injury in PC12 cells was 200 ng/ml in vitro, but excessive leptin diminished this effect. Leptin pretreatment in the MCAO rat model demonstrated a similar effect to previously reported leptin administration post-CIRI. In addition to regulating the expression of inflammation-related cytokines, Western blot analysis showed that leptin pretreatment upregulated BCL-2 and downregulated caspase 3 levels. The MeDIP analysis demonstrated that DNA methylation regulated LEPR gene expression in the MCAO rat model when leptin pretreatment was used.<BR><B>CONCLUSIONS: </B>Exogenous leptin might bind to extra-activated LEPR by reducing the methylation level of the LEPR gene promoter region, which leads to an increase in phosphorylated JAK2/STAT3 and apoptotic signalling pathways.