Thioredoxin1 binding metastasis-associated lung adenocarcinoma transcript 1 attenuates inflammation and apoptosis after intracerebral hemorrhage

Post-transcriptional regulation and RNA-binding proteins (RBPs) play vital roles in the occurrence and secondary injury after intracerebral hemorrhage (ICH) and post-transcriptional regulation, respectively. Therefore, we screened out the differentially expressed RBPs after ICH and found thioredoxin1 (Txn1) as one of the most significantly differentially expressed RBPs. We also used an ICH model and in vitro experiments to investigate the role of Txn1 in clarifying the mechanism of Txn1 in ICH. First, we found that Txn1 was majorly expressed in microglia and neurons in the central nervous system, and its protein level was significantly reduced in perihematoma tissues. Furthermore, we established a Txn1-overexpressing ICH model by stereotaxic injection of adeno-associated virus (AAV) and discovered that the overexpression of Txn1 reduced secondary injury and improved prognosis after ICH. Moreover, to understand the mechanism of Txn1 after ICH, RNA immunoprecipitation combined with high-throughput sequencing (RIP-seq) showed that Txn1 binds to inflammation-and apoptosis-related mRNAs and affects RNA expression through RNA splicing and translational initiation. Finally, RNA pull-down assays and in vitro experiments confirmed that Txn1 binds to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) to reduce inflammation and apoptosis. Collectively, our results show that Txn1 reduces ICH-induced brain injury by affecting the post-transcriptional regulation of MALAT1. Consequently, Txn1 may represent a potential therapeutic target for alleviating ICH-induced brain injury. Overall design: RIP-seq