Transcription Factor TFAP2B Exerts Neuroprotective Effects Targeting BNIP3-Mediated Mitophagy in Ischemia/Reperfusion Injury

Abstract

Cerebral ischemia-reperfusion injury (CIRI) leads to malignant brain edema, blood-brain barrier destruction and neuronal apoptosis. N6-methyladenosine (m6A) RNA modi cation in CIRI has still limited. MeRIP and RNA-sequencing were performed of middle cerebral artery occlusion and reperfusion (MCAO/R) rats to nd novel potential molecular targets. Transcription factor TFAP2B, was standed out of which its m6A abundance decreased associated with a marked reduction of its mRNA based on joint interactive bioinformatics analysis of the MeRIP and RNA-Sequencing data. It was suggeted TFAP2Bcould have an role in CIRI. Functionally, overexpression of TFAP2B in cultrued primary neurons could effectively improve the cell survival and pro-survival autophagy in parallel with reduced cell apoptosis during OGD/R in vitro. Through the RNA-sequencing of TFAP2B overexpressed primary neurons and subsequent validation experiments, it was found that mitophagy receptor BNIP3 was one of an important target of TFAP2B in OGD/R neurons through which TFAP2B could bind to its promoter region for further transcriptional activation of BNIP3, thereby enhancing BNIP3 mediated mitophagy to protect against OGD/R injury of neurons. Lastly, TFAP2B was demonstrated to alleviated the MCAO/R damage to a certain extent in vivo. Although it was failed to con rm TFAP2B dysregulation was m6A dependent in current research, this is the rst study of TFAP2B in CIRI eld with important guiding signi cance.

Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

“…SERPINA1 [521], LRRK2 [649], TF (transferrin) [650], REN (renin) [651], TLR2 [652], MOBP (myelin associated oligodendrocyte basic protein) [653], SYK (spleen associated tyrosine kinase) [654], MBP (myelin basic protein) [625], SHH (sonic hedgehog signaling molecule) [655], RBP4 [590], SNCB (synuclein beta) [543], MMP3 [656], VWF (von Willebrand factor) [657], EGFR (epidermal growth factor receptor) [658], ABCA1 [659] and GPR39 [618] are associated with the clinical stages of dementia. Altered expression of LRRK2 [660], GPR17 [661], TF (transferrin) [662], NEUROD1 [663], RELN (reelin) [664], LCP1 [665], TFAP2B [666], HOXA5 [667], MSR1 [668], REN (renin) [669], OLIG2 [670], TLR2 [671], WT1 [672], SLC22A3 [673], CADM2 [674], PRKCH (protein kinase C eta) [675], MBP (myelin basic protein) [676], XAF1 [677], GPR37 [678], SHH (sonic hedgehog signaling molecule) [679], VTN (vitronectin) [680], SIRT2 [681], RBP4 [682], BMP2 [683], CDH13 [684], NR3C2 [685], TRPC6 [686], MMP3 [687], FGF19 [688], HLA-DRB1 [689], CD74 [690], VWF (von Willebrand factor) [691], ANGPT2 [692], CHRDL1 [693], AKR1C3 [694], NEDD4L [695], CASP1 [696], PDE2A [697], GAS7 [698], TET1 [699], EFNB2 [700], EGFR (epidermal growth factor receptor) [701], ABCA1 [702], PDPN (podoplanin) [703], SLCO1B1 [704], COMT (catechol-O-methyltransferase) [705] and GPR39 [706] have been reported to be associated with stroke. CHRNA4 [707], RELN (reelin) [708], VEGFC (vascular endothelial growth factor C) [709], FRMPD4 [710], SCN4B [711], SLCO5...…”