Liraglutide inhibits AngII-induced cardiac fibroblast proliferation and ECM deposition through regulating miR-21/PTEN/PI3K pathway.

Abstract

BACKGROUND:

Cardiac fibrosis characterized with the aberrant proliferation of cardiac fibroblasts and extracellular matrix (ECM) deposition is a major pathophysiological feature of atrial fibrillation (AF). Liraglutide has exerted an alleviative role in various cardiovascular diseases, and can also regulate the level of microRNAs (miRNAs). It has been reported that miR-21 modulated cardiac fibrosis in AF. However, the regulative effect of liraglutide on atrial fibrosis via miR-21 and the underlying mechanism are still unclear.

METHODS:

The atrial fibroblasts were isolated from the heart of C57BL/6 mice, and treated with Angiotensin II (AngII) and liraglutide. The proliferation, migration, and ECM deposition were determined by cell counting Kit-8 (CCK-8), Brdu, transwell assay, cell scratch, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot and immunofluorescence. The underlying mechanism was explored after transfection of miR-21 mimics into cells.

RESULTS:

Liraglutide inhibited proliferation, migration, invasion of fibroblast cell and ECM deposition in AngII-stimulated cardiac fibroblasts. Additionally, liraglutide decreased the AngII-induced increase in the expression level of miR-21, but enhanced the expression of phosphatase and tensin homolog (PTEN), a target of miR-21, thereby suppressing the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Rescue assay confirmed that overexpression of miR-21 counteracted the ameliorative effect of liraglutide on the proliferation, migration, invasion and ECM deposition in fibroblasts stimulated by AngII.

CONCLUSIONS:

Liraglutide dampened AngII-induced proliferation and migration, and ECM deposition of cardiac fibroblast via modulating miR-21/PTEN/PI3K pathway.

• Authors: Jun Wang, Run Guo, Xiaoli Ma, Ying Wang, Qianyu Zhang, Nan Zheng, Jun Zhang, Chenchen Li
• Journal: Cell and tissue banking (Cell Tissue Bank) Vol. 24 Issue 1 Pg. 125-137 (Mar 2023) ISSN: 1573-6814 [Electronic] Netherlands
• PMID: 35792987 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• Phosphatidylinositol 3-Kinase
• Phosphatidylinositol 3-Kinases
• Angiotensin II
• Liraglutide
• Proto-Oncogene Proteins c-akt
• MicroRNAs

Topics

• Mice
• Animals
• Phosphatidylinositol 3-Kinase (metabolism, pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism, pharmacology)
• Angiotensin II (metabolism, pharmacology)
• Liraglutide (metabolism, pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism, pharmacology)
• Mice, Inbred C57BL
• MicroRNAs
• Extracellular Matrix (metabolism)
• Cell Proliferation
• Fibroblasts (metabolism)
• Fibrosis
• Cell Movement