Hsph1 alleviates hypoxia-glucose deprivation-induced cardiomyocyte damage by regulating endoplasmic reticulum stress

This study investigates how heat shock protein Hsph1 regulates endoplasmic reticulum stress (ERS) in myocardial ischemia-reperfusion injury (MIRI), aiming to identify new targets for MIRI intervention.

RNA-seq analyzed transcriptome changes in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated H9C2 cardiomyocytes, screening differentially expressed genes and conducting GSEA enrichment. Hsph1 knockdown/overexpression models were established. Transmission electron microscopy, Western blot, AM/PI staining, ROS measurement, flow cytometry, Co-IP, and rescue experiments were used to explore Hsph1's role in ERS and apoptosis.

RNA-seq showed OGD/R significantly upregulated Hsph1 and enriched the endoplasmic reticulum protein processing pathway. Hsph1 knockdown disrupted endoplasmic reticulum ultrastructure and promoted apoptosis; overexpression improved OGD/R-induced cell activity decline. Co-IP and rescue experiments confirmed Hsph1 interacts with Hspa5 to regulate the ERS pathway, alleviating cellular stress.

This study first revealed that Hsph1, as a molecular chaperone, maintains endoplasmic reticulum homeostasis and inhibits apoptosis induced by excessive ERS through synergistic interaction with Hspa5, providing a theoretical basis and potential target for developing new therapeutic strategies to alleviate myocardial I/R injury.