SOCS2 exacerbates myocardial injury induced by ischemia/reperfusion in diabetic mice and H9c2 cells through inhibiting the JAK-STAT-IGF-1 pathway.

Aims This study aimed to investigate potential candidates and molecular mechanisms of myocardial ischemia/reperfusion (I/R) injury (MIRI) in type 2 diabetes mellitus. Main methods Type 2 diabetic and myocardial I/R mouse models were established with a high fat-diet (HFD) for 24 weeks and subjecting to global ischemia/reperfusion for 1 h/3 h, respectively. Microarray analysis was applied to screen differentially expressed genes (DEGs) in the hearts of these mice. Moreover, H9c2 cells were treated with high glucose (HG) and/or hypoxia and reoxygenation (H/R). Subsequently, the expression of suppressor of cytokine signaling 2 (SOCS2) was knocked down by siRNA followed by the above treatments. Then, the cell lipid peroxidation and apoptosis-related indicators (malondialdehyde, MDA, and lactate dehydrogenase, LDH, cleaved-caspase-3; glucose-regulated protein 78, GRP78;), Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway-related proteins (p-JAK2 and p-STAT5b) and insulin-like growth factor-1 (IGF-1) were detected. Key findings The mRNA levels of selected DEGs, such as Angptl4 , Gadd45b , Rnf122 and SOCS2 , showed a high degree of correlation with the microarray data. In addition, the levels of SOCS2, caspase-3, GRP78, LDH and MDA were increased, while the IGF-1 level was down-regulated in cells treated with HG and/or H/R compared to untreated cells ( p < 0.05). However, SOCS2 knockdown elevated the expression levels of IGF-1, p-JAK2 and p-STAT5b, as well as caspase-3, GRP78, LDH and MDA. Significance This research suggests that overexpressed SOCS2 might exacerbates MIRI in type 2 diabetes mellitus by inhibiting the expression of IGF-1 via the JAK-STAT signaling pathway. [ABSTRACT FROM AUTHOR]