TAK-242 Protects Against Oxygen-glucose Deprivation And Reoxygenation-induced Injury In Brain Microvascular Endothelial Cells And Alters The Expression Pattern Of IncRNAs

Objective:Background: In our previous study,we found that oxygen-glucose deprivation and reoxygenation(OGD/R)activated toll-like receptor 4(TLR4)signaling in brain microvascular endothelial cells(BMECs),and induced pyroptosis and inflammation.In this study,we aimed to study the effects of ethyl(6R)-6-[N-(2-Chloro-4fluorophenyl)sulfamoyl] cyclohex-1-ene-1-carboxylate(TAK-242)on BMECs under OGD/R.Methods:Methods: Cell viability,inflammatory factors,inflammation-associated pyroptosis,and nuclear factor-κB(NF-κB)signaling were determined using Cell Counting Kit-8(CCK-8)assay,enzyme-linked immunosorbent assay(ELISA),and western blotting,respectively.Long non-coding RNAs(lnc RNAs)and messenger RNAs(m RNAs)expression patterns were profiled with RNA deep sequencing.Moreover,lnc RNAs-encoded short peptides were identified and quantified using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Results:Results: TAK-242 promoted OGD/R cell viability,decreased OGD/R-induced inflammatory factors secretion,and activated the pathways of TLR4/NLRP3/Caspase-1 and TLR4/NF-κB.In addition,AABR07000411.1,AABR070006957.1,and AABR070008256.1 were decreased in OGD/R cells compared with controls,but TAK-242 restored their expression under OGD/R condition.AABR07000473.1,AC130862.4,and LOC10254972.6 were induced by OGD/R,but were suppressed in TAK242+OGD/R cells compared with OGD/R.Moreover,AABR07049961.1,AC127076.2,AABR07066020.1,and AABR07025303.1-encoded short peptides were dysregulated in OGD/R cells,and TAK-242 attenuated the dysregulation of AABR07049961.1,AC127076.2,and AABR07066020.1-encoded short peptides.Conclusion:Conclusions: TAK-242 alters the expression pattern of lnc RNAs in OGD/R cells,and differently expressed lnc RNAs may exert a protective effect against OGD/R injury through a mechanism of competing endogenous RNA(ce RNA)and encoding short peptides.