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1.
Artigo em Inglês | MEDLINE | ID: mdl-38117422

RESUMO

In diabetic patients, concomitant cardiovascular disease is the main factor contributing to their morbidity and mortality. Diabetic cardiomyopathy (DCM) is a form of cardiovascular disease associated with diabetes that can result in heart failure. Transforming growth factor-ß (TGF-ß) isoforms play a crucial role in heart remodeling and repair and are elevated and activated in myocardial disorders. Alterations in certain microRNAs (miRNA) are closely related to diabetic cardiomyopathy. One or more miRNA molecules target the majority of TGF-ß pathway components, and TGF-ß directly or via SMADs controls miRNA synthesis. Based on these interactions, this review discusses potential cross-talk between TGF-ß signaling and miRNA in DCM in order to investigate the creation of potential therapeutic targets.

2.
Toxicology ; 476: 153252, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35792203

RESUMO

Diabetic cardiomyopathy (DCM) is a common heart disease in patients with diabetes mellitus (DM), and is sometimes its main cause of death. Among all the causes of DCM, myocardial cell death is considered to be the most basic pathological change. Furthermore, studies have shown that pyroptosis, the pro-inflammatory programmed cell death, contributes to the progress of DCM. MicroRNAs (miRNAs) also have been proved to take part in the formation of DCM. However, it is not clear whether and how miRNAs regulate myocardial cell pyroptosis in DCM development. In our study, the results showed that the expression of miR-223-3p was significantly increased in cardiomyocytes induced by high glucose, whereas the down-regulation of miR-223-3p weakened it. To understand the signal transduction mechanism of miR-223-3p leading to pyroptosis, we found inhibition of miR-223-3p expression down-regulated caspase-1, pro-inflammatory cytokines IL-1ß and other pyroptosis-associated poteins. Moreover, miR-223-3p repressed SPI1 expression. Furthermore, we silenced SPI1 with siRNA to mimic the effect of miR-223-3p, up-regulating the expression of caspase-1 and resulting to pyroptosis. The above findings inspired us to propose a new signaling pathway to regulate scoria of cardiomyocytes under hyperglycemia: miR-223-3p↑→ SPI1↓→ caspase-1↑ → IL-1ß and other pyroptosis-associated poteins↑→ pyroptosis↑. In summary, miR-223-3p could be a potential therapeutic target for DCM.


Assuntos
Cardiomiopatias Diabéticas , MicroRNAs , Caspase 1/genética , Caspase 1/metabolismo , Caspase 1/farmacologia , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Miócitos Cardíacos , Piroptose
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