Inhibition of miR-223 attenuates the NLRP3 inflammasome activation, fibrosis, and apoptosis in diabetic cardiomyopathy

Xu，Dan1; Zhang，Xiuzhen1; Chen，Xuan1; Yang，Shufen1; Chen，Hongmei2

2020-09-01

10.1016/j.lfs.2020.117980

LIFE SCIENCES   影响因子和分区

0024-3205

1879-0631

Diabetic cardiomyopathy (DCM) is an independent and specific cardiomyopathy, which is associated with cardiac failure in diabetic patients. Currently, the pathogenesis of DCM is a popular research topic in the investigation of cardiovascular diseases. MicroRNAs (miRNAs) have been identified as the latent therapeutic targets for DCM. However, the functions and complex mechanisms of miRNAs in DCM have not been clarified. The cardiomyocyte injury model was established using high glucose (HG) ingestion, and the DCM rat model was established using 30 mg/kg streptozotocin. MicroRNA-223 (miR-223) expression was determined using qRT-PCR; the levels of NLRP3 inflammasome, fibrosis, and apoptosis-related genes and proteins were analyzed using qRT-PCR and western blot assays. Besides the morphological changes and fibrosis of myocardial tissues were evaluated using H&E and Masson staining. We discovered that miR-223 was highly expressed in the HG-induced cardiomyocyte injury model, and miR-223 inhibitor could further relieve the myocardial fibrosis and apoptosis, and inhibit NLRP3 inflammasome of HG-induced H9c2 cells. Additionally, we found that inhibition of miR-223 had obvious positive effects on the cardiac dysfunction and reduced the elevation of blood sugar in the DCM model rats. We found that the miRNA-223 inhibitor could improve the morphological structure and the degree of fibrosis in myocardial tissues in the DCM model rats. Moreover, we verified that inhibition of miR-223 could suppress the NLRP3 inflammasome activation, and alleviate myocardial fibrosis and apoptosis of the DCM model rats. In conclusion, our results suggested that miR-223 might be an underlying therapeutic target for DCM by reducing NLRP3 inflammasome activation, fibrosis, and apoptosis.

Apoptosis Diabetic cardiomyopathy Fibrosis microRNA-223 NLRP3 inflammasome

SCI

英语

第一 ; 通讯

Science and Technology Plan of Shenzhen[JCYJ20180305163833160] ; Science and Technology Plan of Guangzhou[201707010330]

Research & Experimental Medicine ; Pharmacology & Pharmacy

Medicine, Research & Experimental ; Pharmacology & Pharmacy

WOS:000560767000021

PERGAMON-ELSEVIER SCIENCE LTD

BIOLOGY & BIOCHEMISTRY

2-s2.0-85086579226

Scopus

1.Department of Endocrinology and Metabolism,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University; The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,518020,China
2.Department of Endocrinology,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou,510080,China

Xu，Dan,Zhang，Xiuzhen,Chen，Xuan,et al. Inhibition of miR-223 attenuates the NLRP3 inflammasome activation, fibrosis, and apoptosis in diabetic cardiomyopathy[J]. LIFE SCIENCES,2020,256.

Xu，Dan,Zhang，Xiuzhen,Chen，Xuan,Yang，Shufen,&Chen，Hongmei.(2020).Inhibition of miR-223 attenuates the NLRP3 inflammasome activation, fibrosis, and apoptosis in diabetic cardiomyopathy.LIFE SCIENCES,256.

Xu，Dan,et al."Inhibition of miR-223 attenuates the NLRP3 inflammasome activation, fibrosis, and apoptosis in diabetic cardiomyopathy".LIFE SCIENCES 256(2020).