RESUMO
Increasing evidences have revealed the important role of circular RNAs (circRNAs) in cardiovascular system disease. Whereas, the expression profiles and in-depth regulation of circRNAs on vascular smooth muscle cells (VSMCs) is still undetermined. In present study, our research team performed circRNAs microarray analysis to present the circRNAs expression profiles in high glucose induced VSMCs in vitro. Results showed that total of 983 circRNAs were discovered to be differentially expressed, and of these, 458 were upregulated and 525 were downregulated. Moreover, 31 circRNAs were up-regulated and 22 circRNAs were down-regulated with 2 fold change (P < 0.05). One of an up-regulated circRNA, circWDR77, was identified. In vitro cell assay, circWDR77 silencing significantly inhibited the proliferation and migration. Bioinformatics methods discovered that miR-124 and fibroblast growth factor 2 (FGF-2) were downstream targets of circWDR77. The RNA sequence complementary binding was validated by RNA immunoprecipitation (RIP) and/or luciferase reporter assay. Further function validation experiments revealed that circWDR77 regulated VSMCs proliferation and migration via targeting miR-124/FGF2. Taken together, present study firstly reveals the circRNAs expression profiles in high glucose induced VSMCs and identifies the role of circWDR77-miR-124-FGF2 regulatory pathway in VSMCs proliferation and migration, which might provide a new theoretical basis for diabetes mellitus correlated vasculopathy.
Assuntos
Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , RNA/genética , RNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Sequência de Bases , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Células Cultivadas , Células HEK293 , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , RNA Circular , TranscriptomaRESUMO
The present study aimed to investigate whether diminazene attenuates myocardial infarction (MI) in rats. In addition, the present study investigated whether ACE2 signaling was involved in the effects of diminazene on protein function. A rat model of acute myocardial infarction (AMI) was established by occlusion of the left anterior descending coronary artery. The AMI model rats received intraperitoneal injections of diminazene (5 mg/kg/day) for 3 days. Treatment with diminazene significantly inhibited the expression of casein kinase and lactate dehydrogenase, and reduced infarct size in AMI rats. The findings indicated that diminazene significantly reduced the levels of inflammatory factors including tumor necrosis factorα and interleukin6, suppressed the protein expression of cytochrome c oxidase subunit 2 (COX2) and inducible nitric oxide synthase (iNOS), and activated angiotensinconverting enzyme 2 (ACE2), angiotensin II receptor type 1 (AT1R) and MAS1 protooncogene, G proteincoupled receptor (MasR) protein expression in AMI model rats. In conclusion, the present study demonstrated that diminazene attenuated AMI in rats via suppression of inflammation, reduction of COX2 and iNOS expression, and activation of the ACE2/AT1R/MasR signaling pathway.
