A novel function of ATF3 in suppression of ferroptosis in mouse heart suffered ischemia/reperfusion

Liu, Haiqiong; Mo, Huaqiang; Yang, Chaobo; Mei, Xiheng; Song, Xudong; Lu, Wenjie; Hua, Xian-Sheng; Yan, Jianyun; Wang, Xiaochang C.; Yan, Jing; Luo, T.; Lin, Yu-Hao; Wen, Dao-Jun; Chen, Guiming; Chen, Aihua; Ling, Yuanna

doi:10.1016/j.freeradbiomed.2022.07.006

Cited by 46 publications

(29 citation statements)

References 43 publications

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“…Wang et al have found that quercetin relieves acute kidney injury through inhibiting ATF3-mediated ferroptosis ( Wang Y. et al, 2021 ). Liu H. et al (2022) have revealed that ATF3 inhibits the ferroptosis of myocardial cells following ischemia/reperfusion injury. The above evidence indicates the possibility of ferroptosis involving in the action mechanisms of ATF3 in IS.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of ATF3 suppresses the progression of ischemic stroke through inhibiting ferroptosis

Zhang

et al. 2023

Front. Mol. Neurosci.

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ObjectiveCurrent therapies towards ischemic stroke (IS) are still not satisfied, and alternative strategies targeting ferroptosis may be another choice. The purpose of this study is to screen potential ferroptosis-related genes involving in IS.MethodsA rat model of IS was established via middle cerebral artery occlusion. Differentially expressed genes (DEGs) were screened from the model rats through transcriptional sequencing. Among the isolated DEGs, the expression of several attractive DEGs relating with ischemic injury was confirmed by qRT-PCR. Then, ATF3 relating with both IS and ferroptosis was selected a candidate gene for functional assays. After knockdown of ATF3 in the model rats, the infarction, histopathology, apoptosis, and ferroptosis in brain tissues were evaluated.ResultsIS model was successfully established in rats, exhibiting the emergence of infarction area, histopathological injury, and enhanced cell apoptosis. Total 699 up-regulated DEGs and 461 down-regulated DEGs were screened from the model rats. qRT-PCR verified the up-regulation of Hspa1b, Tfpi2, Ptx3, and Atf3, and the down-regulation of Smyd1 and Tacr2 in the Model group compared with those in the Sham group. It is noteworthy that knockdown of ATF3 decreased the infarction area, relieved histopathological injury, weakened apoptosis, and inhibited ferroptosis in the model rats.ConclusionSeveral candidate genes in relation with IS were revealed. More importantly, knockdown of ATF3 may relieve IS through inhibiting ferroptosis.

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Section: Discussionmentioning

confidence: 99%

Knockdown of ATF3 suppresses the progression of ischemic stroke through inhibiting ferroptosis

Zhang

et al. 2023

Front. Mol. Neurosci.

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“…However, only one study showed that ATF3 silencing could inhibit tert-Butyl Hydroperoxide-(TBHP-) induced IDD by inhibiting ferroptosis of nucleus pulposus cells [37]. Further, overexpression of ATF3 inhibits cardiomyocytes' ferroptosis induced by erastin and RSL3 [38]. In addition, ATF3 is a key transcriptional regulator and inhibits inflammatory response [39].…”

Section: Discussionmentioning

confidence: 99%

Establishment of Ferroptosis-Related Key Gene Signature and Its Validation in Compression-Induced Intervertebral Disc Degeneration Rats

Guo

Yang

Niu

et al. 2023

Oxidative Medicine and Cellular Longevity

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Cell death and functional loss of nucleus pulposus cell play essential roles in intervertebral disc degeneration (IDD). Ferroptosis is a newly identified cell death type, and its role in IDD is still under investigation. Identifying the key genes of ferroptosis in IDD helps to identify the therapeutic targets of IDD. In this study, we downloaded the human IDD mRNA microarray data from the Gene Expression Omnibus and ferroptosis genes from FerrDb, then performed a series of analyses using strict bioinformatics algorithms. In general, we obtained 40 ferroptosis-related differential expression genes (FerrDEGs) and identified six ferroptosis key gene signatures, namely, ATF3, EIF2S1, AR, NQO1, TXNIP, and AKR1C3. In addition, enrichment analysis of the FerrDEGs was conducted, the protein-protein interaction network was constructed, the correlations between ferroptosis key genes and immune infiltrating cells were analyzed, and the lncRNA-miRNA-mRNA ceRNA network was constructed. In particular, ATF3 and EIF2S1 showed the strongest correlation with immune cell function, which might lead to the development of IDD. Finally, the expressions of ferroptosis key genes were verified in the rat compression-induced IDD. In conclusion, this preliminary study analyzed and verified the mechanism of ferroptosis in IDD, laid a foundation for the follow-up study of the mechanism of ferroptosis in IDD, and provided new targets for preventing and delaying IDD.

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“…Using mouse RIRI model, ATF3 was found to be speci cally expressed in the outer stripe of medulla, which was in ltrated by neutrophils, indicating that ATF3 may be involved in the cross-talk between renal epithelial cells and immune cells [23]. In addition, ATF over-expression in mice inhibited ferroptosis and rescued IR injury of heart [24]. ATF4, another activating transcription factor, also acts as an important player in IRI of different organs.…”

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes in patients with renal ischemia-reperfusion injury

Jiang

Chen

et al. 2023

Preprint

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Background Effective and curable treatment for kidney injury caused by renal ischemia/reperfusion (I/R) have been poor reported. Severe inflammation and ferroptosis resulting from the formation of reactive oxygen species (ROS)，is the main cause of kidney injury. Thus, identify the biomarkers associated with ferroptosis in renal ischemia-reperfusion injury (RIRI) is emergency and crucial. Methods Bioinformatics analysis was used to discover differentially expressed genes (DEGs) from the GSE43974 dataset. Differentially expressed ferroptosis-related genes were discovered as the intersection of DEGs and ferroptosis-related genes (DEFRGs). Using the "clusterProfiler" R package, gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were done on DEFRGs. The Cytoscape plugin Molecular Complex Detection (MCODE)was used to extract hub genes from a protein-protein interaction (PPI) network. Finally, regulatory networks for TF-hub genes and miRNA-hub genes were predicted and created using the miRNet software. Results There found a total of 3,950 DEGs between the RIRI and control samples. After taking the intersection of DEGs and ferroptosis-related genes, 74 DEFRGs are obtained. DEFRGs were enriched in reaction to oxidative stress, cellular response to chemical stress, response to nutritional levels, and cellular response to oxidative stress, according to the GO analysis. The KEGG enrichment analysis revealed that these DEFRGs were substantially related with the mitophagy-animal, kaposi sarcoma-associated herpesvirus infection, autophagy-animal, and IL17 signaling pathways. MCODE found ATF3, ATF4, ATG3, ATG5, BECN1, DDIT3, HSPA5, NFE2L2, WIPI1, and XBP1 as the hub genes. Finally，the receiver operating characteristic (ROC) analysis of the GSE43974 data set reveals ATF3, DDIT3, ATF4, and ATG3 with AUC greater than 0.70,which were identified as the biomarkers related RIRI. Conclusion ATF3, DDIT3, ATF4, and ATG3 were identified as ferroptosis-related hub genes and proven to have diagnostic value for RIRI.

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A novel function of ATF3 in suppression of ferroptosis in mouse heart suffered ischemia/reperfusion

Cited by 46 publications

References 43 publications

Knockdown of ATF3 suppresses the progression of ischemic stroke through inhibiting ferroptosis

Knockdown of ATF3 suppresses the progression of ischemic stroke through inhibiting ferroptosis

Establishment of Ferroptosis-Related Key Gene Signature and Its Validation in Compression-Induced Intervertebral Disc Degeneration Rats

Identification of ferroptosis-related genes in patients with renal ischemia-reperfusion injury

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