RESUMO
INTRODUCTION: Arterial calcification is a major factor for cardiovascular events and is characterized by vascular smooth muscle cells (VSMCs) transformed into osteoblast-like cells. Long non-coding RNAs (lncRNA) were recognized as important regulators of diverse biological processes. Previous studies have demonstrated that lncRNAs could regulate the proliferation and apoptosis of VSMCs. LncRNA-ANCR (Anti-differentiation ncRNA) is an essential mediator governing the differentiation of human osteoblast. However, it is unclear whether ANCR could regulate the osteoblastic differentiation of VSMCs. In this study, we determined the effect of ANCR on VSMCs differentiation and arterial calcification. MATERIALS AND METHODS: Both cellular and mouse model of arterial calcification were, respectively, established to investigate the role of ANCR in the mechanism of arterial calcification. ANCR overexpressing lentivirus were used to investigate the effects of ANCR on the expression of bone proteins and autophagy-related molecules. RESULTS: ANCR could inhibit ß-glycerophosphate (ß-GP)-induced VSMCs osteoblastic differentiation and mineralization due to decreased expressions of Runt-related transcription factor 2, bone morphogenetic protein-2, and formation of mineralized nodule, and attenuate high calcitriol-induced mice model of arterial calcification. Furthermore, ANCR could significantly increase LC3 and autophagy protein 5 expression in ß-GP-stimulated VSMCs, and the effect could be inhibited by 3-methyladenine, a pharmacological inhibitor of autophagy. CONCLUSION: ANCR may inhibit the osteoblastic differentiation of VSMCs and attenuate mice arterial calcification through activating autophagy.
Assuntos
Substâncias Protetoras/metabolismo , RNA Longo não Codificante/metabolismo , Calcificação Vascular/genética , Animais , Apoptose/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Calcitriol , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Glicerofosfatos/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , RNA Longo não Codificante/genéticaRESUMO
A highly efficient IrIII -catalyzed cascade cyclization of indoles and diazoes giving access to unique pentacyclic-fused carbazoles has been developed. This novel strategy expanded the application scope of coupling partners to take diazo compounds as a C2 source, and two new cycles, three new C-C and one new C-N bonds were formed in one-pot.