The Mechanisms Of SFRP5 In Improving Diabetic Cardiomyocyte Injury By Inhibiting The Inflammation And Pyroptosis

BackgroundMinimizing the risk of cardiovascular complications has been set as the main purpose of the management for high blood glucose levels in patients with type 2 diabetes mellitus(T2DM)and cardiovascular diseases by the current guidelines.Instead of the canonical hypoglycemic drugs,some emerging medicines,such as Sodium-Glucose Cotransporter 2(SGLT2)inhibitors and Glucagon-like Peptide 1(GLP1)receptor agonists can reduce the risk of cardiovascular disease in patients with T2DM to an extent.In spite of it,it’s still significant to find a more effective therapeutic regimen for DM patients.Diabetic cardiomyopathy(DCM),as one of the most important complications of diabetes mellitus(DM),greatly increases the morbidity and mortality of DM patients.With numerous preclinical and clinical evidence,there are still no effective diagnostic criteria and therapeutic strategies to improve DCM in clinical practice.Therefore,it’s of great significance to find new therapeutic targets for DCM.Secreted frizzled-related protein 5(SFRP5),as an anti-inflammatory adipokine,has a positive effect on diabetes and cardiovascular diseases.By regulating inflammation and pyroptosis,SFRP5 inhibits the pathogenesis of a variety of clinical diseases.Although studies have shown the protective effects of SFRP5 on the myocardium,the mechanisms of it keep unknown.Wnt5a is an important inflammatory factor and the Wnt5a/JNK signaling pathway plays an important role in the progression of DM and its related cardiovascular complications.SFRP5 takes part in the regulation of non-canonical Wnt signaling pathways,which could be able to reduce inflammation by inhibiting the Wnt5a.Therefore,we proposed that SFRP5 may improve the inflammatory and pyroptosis of T2DM patients by antagonizing the Wnt5a/JNK signaling pathway,and plays a protective role for cardiomyocytes in the progression of T2DM.ObjectivesThis study aims to certify that the inflammation and pyroptosis are associated with DCM,verify that SFRP5 plays a protective effect by inhibiting the inflammation and pyroptosis of cardiomyocytes,and prove that the effects of SFRP5 are related to the inhibition of Wnt5a/JNK signaling pathway.MethodsCCK8 assay was used to examine the cell viability in vitro.The expression of SFRP5 in H9C2 was detected by q-RT-PCR and Western Blot.q-RT-PCR was used to investigate the expression of inflammatory factors:TNF-α,IL-1β,IL-6,IL-18,and Western Blot was used to detect the expression of GSDMD,Caspase-1,and NLRP3.The effects of SFRP5 on the Wnt5a/JNK signaling pathway were detected by Western Blot.Results1.Glucose and palmitic can induce the inflammation and pyrolysis of H9C2 cells(both P<0.05)and cell viability was decreased(both P<0.05)in DCM model cells.The expression of SFRP5 was also significantly reduced in DCM cells(both P<0.05).2.Overexpression of SFRP5 can improve the viability of H9C2 cells(both P<0.05)and inhibit the inflammatory and pyrolysis of cardiomyocytes(both P<0.05),while knock-down of SFRP5 has the opposite effect(both P<0.05).3.Overexpression of SFRP5 inhibited the Wnt5a/JNK signaling pathway,reducing the expression of Wnt5a and the phosphorylation of JNK(P<0.05),while knock-down SFRP5 can activate the Wnt5a/JNK signaling pathway(P<0.05).ConclusionsOur results showed that the inhibitory effects of SFRP5 on inflammatory and pyrolysis can improve the viability of H9C2 through the inhibition of the Wnt5a/JNK signaling pathway.SFRP5 plays an important role in protecting cardiomyocytes and it is a promising target for the treatment of DCM.