Pathophysiology Department, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, and The Second Affiliated Hospital, Hengyang Medical School,University of South China, Hengyang City, Hunan Province 421001, PR China.
Pathophysiology Department, Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, and The Second Affiliated Hospital, Hengyang Medical School,University of South China, Hengyang City, Hunan Province 421001, PR China.
Toxicology. 2022 Jun 30;476:153252. doi: 10.1016/j.tox.2022.153252. Epub 2022 Jul 2.
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-1β 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-1β and other pyroptosis-associated poteins↑→ pyroptosis↑. In summary, miR-223-3p could be a potential therapeutic target for DCM.
糖尿病心肌病（DCM）是糖尿病患者（DM）常见的心脏病，有时是其主要死亡原因。在 DCM 的所有病因中，心肌细胞死亡被认为是最基本的病理变化。此外，研究表明，促炎程序性细胞死亡的细胞焦亡有助于 DCM 的进展。microRNAs（miRNAs）也被证明参与了 DCM 的形成。然而，miRNAs 是否以及如何调节 DCM 发展中心肌细胞的细胞焦亡尚不清楚。在我们的研究中，结果表明，高糖诱导的心肌细胞中 miR-223-3p 的表达明显增加，而 miR-223-3p 的下调减弱了它。为了了解 miR-223-3p 导致细胞焦亡的信号转导机制，我们发现抑制 miR-223-3p 的表达下调了半胱氨酸蛋白酶-1（caspase-1）、促炎细胞因子 IL-1β 和其他与细胞焦亡相关的蛋白。此外，miR-223-3p 抑制 SPI1 的表达。此外，我们用 siRNA 沉默 SPI1 来模拟 miR-223-3p 的作用，上调 caspase-1 的表达，导致细胞焦亡。上述发现启发我们提出了一个新的信号通路来调节高糖环境下心肌细胞的焦亡：miR-223-3p↑→SPI1↓→caspase-1↑→IL-1β 和其他与细胞焦亡相关的蛋白↑→细胞焦亡↑。总之，miR-223-3p 可能是 DCM 的一个潜在治疗靶点。
Zotero 插件