Mengting Sheng1, Zirui Huang2, Liming Pan2, Min Yu1, Cai Yi3, Lin Teng4, Ling He5, Chen Gu6, Chunli Xu7, Junming Li8. 1. Department of Intensive Care Unit (ICU), the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang 443000, China. 2. Department of Cardiology, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang 443000, China. 3. Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, China. 4. Department of Cardiology, the First College of Clinical Medical Sciences of Three Gorges University/Central People's Hospital of Yichang, Yichang 443000, China. 5. Department of Geriatrics, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang 443000, China. 6. Department of B ultrasound room, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang 443000, China. 7. Department of Inspection office, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang 443000, China. 8. Department of Cardiology, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang 443000, China. Electronic address: lijunming@medmail.com.cn.
Abstract
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 24weeks and subjecting to global ischemia/reperfusion for 1h/3h, 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.
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 24weeks and subjecting to global ischemia/reperfusion for 1h/3h, 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.
Authors: Andrea Coppola; Giada Zorzetto; Filippo Piacentino; Valeria Bettoni; Ida Pastore; Paolo Marra; Laura Perani; Antonio Esposito; Francesco De Cobelli; Giulio Carcano; Federico Fontana; Paolo Fiorina; Massimo Venturini Journal: Acta Diabetol Date: 2021-11-15 Impact factor: 4.280