MircroRNA-145 Attenuates Cardiac Fibrosis Via Regulating Mitogen-Activated Protein Kinase Kinase Kinase 3.

Abstract

PURPOSE:

This study aimed to explore the effect of microRNA (miR)-145 on cardiac fibrosis in heart failure mice and its target.

METHODS:

Experiments were carried out in mice receiving left coronary artery ligation, transverse aortic constriction (TAC), or angiotensin (Ang) II to trigger heart failure, and in cardiac fibroblasts (CFs) with Ang II-induced fibrosis.

RESULTS:

The miR-145 levels were decreased in the mice hearts of heart failure induced by myocardial infarction (MI), TAC or Ang II infusion, and in the Ang II-treated CFs. The impaired cardiac function was ameliorated by miR-145 agomiR in MI mice. The increased fibrosis and the levels of collagen I, collagen III, and transforming growth factor-beta (TGF-β) in MI mice were inhibited by miR-145 agomiR or miR-145 transgene (TG). The agomiR of miR-145 also attenuated the increases of collagen I, collagen III, and TGF-β in Ang II-treated CFs. Bioinformatics analysis and luciferase reporter assays indicated that mitogen-activated protein kinase kinase kinase 3 (MAP3K3) was a direct target gene of miR-145. MAP3K3 expression was suppressed by MiR-145 in CFs, while the MAP3K3 over-expression reversed the inhibiting effects of miR-145 agomiR on the Ang II-induced increases of collagen I, collagen III, and TGF-β in CFs.

CONCLUSION:

These results indicated that miR-145 upregulation could improve cardiac dysfunction and cardiac fibrosis by inhibiting MAP3K3 in heart failure. Thus, upregulating miR-145 or blocking MAP3K3 can be used to treat heart failure and cardiac fibrosis.

• Authors: Yun Liu, Jing Hu, Weiwei Wang, Qian Wang
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 37 Issue 4 Pg. 655-665 (08 2023) ISSN: 1573-7241 [Electronic] United States
• PMID: 35416554 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• MicroRNAs
• MAP Kinase Kinase Kinase 3
• Collagen
• Transforming Growth Factor beta
• Angiotensin II
• Transforming Growth Factor beta1

Topics

• Mice
• Animals
• Myocardium (pathology)
• MicroRNAs (genetics, metabolism)
• MAP Kinase Kinase Kinase 3 (metabolism)
• Myocardial Infarction (pathology)
• Heart Failure (metabolism)
• Collagen (metabolism)
• Transforming Growth Factor beta (metabolism)
• Fibrosis
• Angiotensin II (metabolism)
• Transforming Growth Factor beta1 (metabolism)