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1.
Toxicology ; 476: 153252, 2022 06 30.
Article in English | MEDLINE | ID: mdl-35792203

ABSTRACT

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.


Subject(s)
Diabetic Cardiomyopathies , MicroRNAs , Caspase 1/genetics , Caspase 1/metabolism , Caspase 1/pharmacology , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/metabolism , Humans , Inflammasomes/genetics , Inflammasomes/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Myocytes, Cardiac , Pyroptosis
2.
Pharmacol Res ; 173: 105868, 2021 11.
Article in English | MEDLINE | ID: mdl-34481974

ABSTRACT

Diabetes-related cardiovascular disease (CVD) is a global health issue that causes thousands of people's death around the world annually. Diabetes-related CVD is still prevailing despite the progression being made in its diagnosis and treatment. Therefore it is urgent to find therapeutic strategies.to prevent it. MicroRNA (miRNA) is a single-stranded non-coding RNA involved in the process of post-transcriptional control of gene expression in eukaryotes. A large number of literatures reveal that miRNAs are implicated in diabetes-related CVD. The increase of miRNAs in exosomes may promote the occurrence and development of diabetes-related cardiovascular complication. However, some other studies identify that miRNAs in exosomes are supposed to be involved in cardiac regeneration and confer cardiac protection effect. Therefore, targeting the miRNA in exosome is regarded as a potent therapeutic measure to alleviate diabetes-related CVD. In this article, we review current knowledge about the role of exosomal miRNAs in diabetes-related cardiovascular complication, such as coronary heart disease, Peripheral artery disease, stroke, diabetic cardiomyopathy, diabetic nephropathy and diabetic retinopathy. Exosomal miRNAs are considered to be central regulators of diabetes-Related CVD and provide a therapeutic tool for diagnosis and treatment of diabetes-related cardiovascular complication.


Subject(s)
Cardiovascular Diseases/genetics , Diabetes Complications/genetics , Exosomes/genetics , MicroRNAs , Animals , Cardiovascular Diseases/etiology , Cardiovascular Diseases/therapy , Diabetes Complications/therapy , Humans
3.
IUBMB Life ; 72(9): 1870-1878, 2020 09.
Article in English | MEDLINE | ID: mdl-32697419

ABSTRACT

PIWI-interacting RNAs (piRNAs) are a kind of non-coding small RNAs, which play a biological role by specifically binding to PIWI proteins. Studies have demonstrated that piRNAs play a significant role in germline cell growth by repressing transposable elements, especially in the regulation of DNA methylation. Recently increasing evidence revealed that piRNAs involved in the regulation of cell proliferation, apoptosis, and cycle; however, the mechanism of piRNAs is unclear. This review summarizes the research progress regarding the roles of piRNAs in the cell proliferation, apoptosis, and cycle.


Subject(s)
Apoptosis , Cell Cycle , Cell Proliferation , DNA Methylation , DNA Transposable Elements , RNA, Small Interfering/genetics , Animals , Humans
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