RNA-seq based transcriptomic map reveals multiple pathways of necroptosis in treating myocardial ischemia reperfusion injury

• Published in: Gene Vol. 906; p. 148217
• Main Authors: Zhang, Yijia, Song, Qingbiao, E, Sihan, Guan, Xuehao, Zhang, Zhiyu, Juan, Zhaodong, Sun, Xiaotong, Liang, Yingxia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.05.2024
• Subjects: Animals; Apoptosis - genetics; Gene Expression Profiling; Male; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - metabolism; Myocardium - metabolism; Necroptosis; Rats; RNA-Seq; TTC; DMSO; ns; LPS; BP; SD; DEGs; IA; KEGG; MF; RIPK1; CC; RIPK3; MLKL; dscDNA; RIPK2; IL-1; RIPK4; NIA; qRT-PCR; GO; Nec-1; IS; IL-6; TNF-α; NOX; MIRI; Not DEG
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2024.148217

•Necrostatin-1 pretreatment alleviated infract size by regulate the levels of Ripk1 and Ripk3 not the levels of genes RIPK2 and PIPK4.•Necrostatin-1 might be involved in the regulation of cell death and the immune response through Myc, Fos,Egr1 gene.•Activation of the TNF-α/RIPK1/RIPK3 signaling pathway was significant in myocardial ischemia reperfusion injury treated with necrostatin-1. Necroptosis has been shown to contribute to myocardial ischemia reperfusion injury (MIRI). This study aims to gain new insights into the signaling pathway of necroptosis in rat MIRI using RNA sequencing. MIRI was induced in male rats by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 120 min. RNA sequencing was performed to obtain mRNA profiles of MIRI group and MIRI group treated with necrostatin-1 (Nec-1,an inhibitor of necroptosis). Differentially expressed genes (DEGs) were then identified. The DEGs were prominently enriched in the TNF-α signaling pathway, the MAPK signaling pathway and cytokine-cytokine receptor pathways. The majority of the results were associated with genes like Thumpd3,Egr2,Dot1l,Cyp1a1,Dbnl,which primarily regulate inflammatory response and apoptosis, particularly in myocardium. The above results suggested that Nec-1 might be involved in the regulation of necroptosis and the inflammatory response through the above-mentioned genes.