Hmgcs2 regulates M2 polarization of macrophages to repair myocardial injury induced by sepsis

Zou, Xiao-zheng; Hao, Junfeng; Hou, Mingxiao

doi:10.18632/aging.204944

Cited by 4 publications

References 45 publications

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Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Acute kidney injury (AKI) is a type of renal disease occurs frequently in hospitalized patients, which may cause abnormal renal function and structure with increase in serum creatinine level with or without reduced urine output. With the incidence of AKI is increasing. However, the molecular mechanisms of AKI have not been elucidated. It is significant to further explore the molecular mechanisms of AKI. We downloaded the GSE139061 next generation sequencing (NGS) dataset from the Gene Expression Omnibus (GEO) database. Limma R bioconductor package was used to screen the differentially expressed genes (DEGs). Then, the enrichment analysis of DEGs in Gene Ontology (GO) function and REACTOME pathways was analyzed by g:Profiler. Next, the protein-protein interaction (PPI) network and modules was constructed and analyzed, and the hub genes were identified. Next, the miRNA-hub gene regulatory network and TF-hub gene regulatory network were built. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. Overall, 956 DEGs were identified, including 478 up regulated and 478 down regulated genes. The enrichment functions and pathways of DEGs involve primary metabolic process, small molecule metabolic process, striated muscle contraction and metabolism. Topological analysis of the PPI network and module revealed that hub genes, including PPP1CC, RPS2, MDFI, BMI1, RPL23A, VCAM1, ALB, SNCA, DPP4 and RPL26L1, might be involved in the development of AKI. miRNA-hub gene and TF-hub gene regulatory networks revealed that miRNAs and TFs including hsa-mir-510-3p, hsa-mir-6086 and mir-146a-5p, MAX and PAX2, might be involved in the development of AKI. Various known and newtherapeutic targets were obtained via network analysis. The results of the current investigation might be beneficial for the diagnosis and treatment of AKI.

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Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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GCN5L1 regulates glucose and ketone body metabolism during cardiac ischemia-reperfusion injury

Bugga,

Stoner,

Manning

et al. 2024

Preprint

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Ischemic heart diseases are the leading cause of death among cardiovascular diseases. Reperfusion of the ischemic myocardium is the only way to treat IHD. However, reperfusion can damage the ischemic myocardium if it does not happen at the right time. Therefore, understanding the pathophysiology of cardiac ischemic reperfusion injury is essential to identifying new therapeutic targets. We reported the cardioprotective role of GCN5L1 in ex-vivo cardiac ischemic reperfusion injury through the regulation of cytoprotective signaling by reducing oxidative stress. The current study investigated the role of GCN5L1 in in-vivo cardiac ischemic reperfusion injury and in-vitro H/R injury in AC16 cells. The cardiac-specific GCN5L1 KO did not further deteriorate the cardiac function and infarct size. We measured the glucose metabolism-related protein expression among all experimental groups and found that GCN5L1 KO significantly decreases glucose metabolism by PDH phosphorylation. We further evaluated the role of GCN5L1 in in-vitro H/R injury in genetically modified AC16 cells (GCN5L1 KD and overexpressed and control). GCN5L1 KD in AC16 cells promotes phosphorylation of PDH; similarly, overexpression reduces the p-PDH levels. We identified that the regulation of PDH phosphorylation via PDK4/PDP1/PDPR and GCN5L1 regulates the PDK4 expression. We measured the ketone body metabolism related to protein expression in control and KD cells after H/R injury and found the upregulation of ketone body metabolism-related protein expression in KD cells compared to control AC16 cells. Altogether, our in vivo and in vitro studies findings conclude that GCN5L1 is required for glucose metabolism in ischemic reperfusion injury, and in the absence of GCN5L1, ketone body metabolism accomplishes the cardiac energy requirements and prevents I/R induced cardiac damage and infarct size.Graphical AbstractGraphical abstract of the manuscriptAltogether, our results conclude that Cardiomyocyte-specific GCN5L1 KO in-vivo cardiac ischemic reperfusion injury and in-vitro Hypoxia-reoxygenation stress significantly affect glucose metabolism by suppressing glucose metabolism. Cardiac-specific GCN5L1 KO mice in-vivo and knockdown in AC16 cells invitro upregulates the expression of enzymes that are involved in the ketone body metabolism to rescue from in-vivo cardiac ischemic reperfusion injury and invitro H/R stress.

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Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway

Long,

Yang,

Zhou

2024

Open Medicine

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Background Sepsis triggers myocardial injury and dysfunction, leading to a high mortality rate in patients. Cardiomyocyte apoptosis plays a positive regulatory role in septic myocardial injury and dysfunction. However, the mechanism is unclear. Methods Bioinformatics analysis was used to identify differentially expressed genes in septic mice heart and validate key genes and pathways. The correlation of protein–protein and protein–pathway was analyzed. Sequentially, the cecal ligament and puncture (CLP) was used to induce septic mice, followed by Serpine1 inhibitor treatment. Finally, the regulatory relationship of Yes-associated protein1 (YAP1), Serpine1, and caspase-3 was verified in LPS-exposed mouse cardiomyocytes. Results Bioinformatic analysis found that Serpine1 expression is decreased in septic mice heart tissue and closely related to the HIPPO signaling pathway, while YAP1 is negatively correlated with apoptosis. In vivo, CLP induced a reduction of survival rate, cardiac dysfunction, and an increase in Serpine1 and Cleaved Caspase-3 expression, which could be reversed by a Serpine1 inhibitor. In vitro, LPS induced the mouse cardiomyocytes apoptosis, which could be reversed by Serpine1 inhibitor. Silencing YAP1 and Serpine1 reversed the LPS-induced increase in Serpine1 and Cleaved Caspase-3 expression, but silencing Serpine1 did not affect the LPS-induced YAP1 expression. Conclusion Sepsis induced mouse cardiomyocytes apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway.

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Hmgcs2 regulates M2 polarization of macrophages to repair myocardial injury induced by sepsis

Cited by 4 publications

References 45 publications

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

GCN5L1 regulates glucose and ketone body metabolism during cardiac ischemia-reperfusion injury

Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway

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