SIAH1 promotes the pyroptosis of cardiomyocytes in diabetic cardiomyopathy via regulating IκB-α/NF-κB signaling

Abstract

Inflammation-mediated dysfunction of cardiomyocytes is the main cause of diabetic cardiomyopathy (DCM). The present study aimed to investigate the roles of SIAH1 in DCM. RT-qPCR was conducted to detect mRNA levels. ELISA was performed to detect cytokine release. Western blot was used to detect protein expression. LDH assay was used to determine cytotoxicity. In vitro ubiquitination assay was applied to determine the ubiquitination of IκB-α. TUNEL assay was conducted to determine cell death. Flow cytometry was applied for determining cardiomyocyte pyroptosis. The results showed that SIAH1 was overexpressed in human inflammatory cardiomyopathy. High expression of SIAH1 was associated with inflammatory response. SIAH1 was also overexpressed lipopolysaccharide (LPS)-induced inflammatory cardiomyopathy model in vitro. However, SIAH1 knockdown suppressed the inflammatory-related pyroptosis of cardiomyocytes. SIAH1 promoted the ubiquitination of IκB-α and activation of NF-κB signaling, which promoted the pyroptosis of cardiomyocytes. In conclusion, SIAH1 exacerbated the progression of human inflammatory cardiomyopathy via inducing the ubiquitination of IκB-α and activation of NF-κB signaling. Therefore, SIAH1/IκB-α/NF-κB signaling may be a potential target for human inflammatory cardiomyopathy.