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MicroRNA-143-3p promotes human cardiac fibrosis via targeting sprouty3 after myocardial infarction
- Source :
- Journal of Molecular and Cellular Cardiology. 129:281-292
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Myocardial infarction (MI) is one of the most catastrophic diseases threatening human health in the world. Because cardiomyocytes have a minuscule regenerative potential, the natural repair of infarct healing after MI shows fibrotic scar. MicroRNA-143-3p (miR-143-3p) plays a critical regulatory role in various pathophysiological processes in the heart. Sprouty3 (SPRY3) is predicted to be a potential fibrosis-associated target gene of miR-143-3p. The aim was to explore the role and mechanism of miR-143-3p in the infarct healing after MI in vivo and in vitro. Myocardial samples were obtained during autopsy from 12 human patients with or without MI. An increase in miR-143-3p mRNA levels was detected in the infarct zone of human MI samples. Moreover, silencing expression of miR-143-3p by antagomir-143-3p alleviated fibrotic scar in MI model of mice. To assess the mechanism by which miR-143-3p may function in fibrosis, human cardiac fibroblasts (HCFs) were transfected with miR-143-3p mimics and inhibitors. MiR-143-3p overexpression promoted HCFs proliferation, migration, transformation, and extracellular matrix (ECM) excessive accumulation. Additionally, miR-143-3p inhibitors reversed the fibrosis effect of HCFs treated with transforming growth β1 (TGFβ1) in vitro. Importantly, a luciferase reporter assay demonstrated that miR-143-3p could directly bind to the 3'-untranslational region (3'-UTR) of SPRY3 mRNA. Lastly, HCFs transfected with SPRY3 siRNA (si-SPRY3) enhanced the activation of the P38, ERK, and JNK pathways in the process of fibrosis. MiR-143-3p promoted fibrosis along with SPRY3 degradation and the activation of its downstream P38, ERK, and JNK pathways. Our results may contribute to improve the quality of life in MI patients by interfering with the role of miR-143-3p in MI area.
- Subjects :
- Adult
Male
0301 basic medicine
MAPK/ERK pathway
MMP2
MAP Kinase Signaling System
Cardiac fibrosis
p38 mitogen-activated protein kinases
Myocardial Infarction
Down-Regulation
030204 cardiovascular system & hematology
Models, Biological
Transforming Growth Factor beta1
Mice
03 medical and health sciences
0302 clinical medicine
Cell Movement
Fibrosis
microRNA
Animals
Humans
Medicine
Gene silencing
Gene Silencing
Molecular Biology
Cell Line, Transformed
Cell Proliferation
Base Sequence
biology
business.industry
Myocardium
Intracellular Signaling Peptides and Proteins
Fibroblasts
Middle Aged
medicine.disease
Extracellular Matrix
MicroRNAs
030104 developmental biology
Mitogen-activated protein kinase
biology.protein
Cancer research
Female
Collagen
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 00222828
- Volume :
- 129
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular and Cellular Cardiology
- Accession number :
- edsair.doi.dedup.....0c66685fbc20eca2b80454880439ac09