Downregulation of S100A4 Alleviates Cardiac Fibrosis via Wnt/β -Catenin Pathway in Mice

• Published in: Cellular physiology and biochemistry Vol. 46; no. 6; pp. 2551 - 2560
• Main Authors: Qian, LiJun, Hong, Jian, Zhang, YanMei, Zhu, MengLin, Wang, XinChun, Zhang, YanJuan, Chu, Ming, Yao, Jing, Xu, Di
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Adenoviruses; Animals; Cancer; Cardiac fibrosis; Cell cycle; Cell growth; Cell Hypoxia; Cells, Cultured; Down-Regulation; Fibroblasts; Fibrosis; Gene Knockdown Techniques; Hypoxia; Immunoglobulins; Laboratory animals; Male; Medical prognosis; Medical research; Metastasis; Mice; Mice, Inbred C57BL; Myocardial Infarction - genetics; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial infraction; Myocardium - metabolism; Myocardium - pathology; Original Paper; Proteins; S100 Calcium-Binding Protein A4 - analysis; S100 Calcium-Binding Protein A4 - genetics; S100 Calcium-Binding Protein A4 - metabolism; S100A4; Wnt Signaling Pathway; Wnt/β-catenin; United States > US; China; Cardiac fibrosis; S100A4; Myocardial infraction; Mice; Wnt/β-catenin
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000489683

Background/Aims: Cardiac fibrosis is a pathological change leading to cardiac remodeling during the progression of myocardial ischemic diseases, and its therapeutic strategy remains to be explored. S100A4, a calcium-binding protein, participates in fibrotic diseases with an unclear mechanism. This study aimed to investigate the role of S100A4 in cardiac fibrosis. Methods: Cardiac fibroblasts from neonatal C57BL/6 mouse hearts were isolated and cultured. Myocardial infarction was induced by ligating the left anterior descending coronary artery (LAD). The ligation was not performed in the sham group. A volume of 5×10 5 pfu/g adenovirus or 5 µM/g ICG-001 was intramyocardially injected into five parts bordering the infarction zone or normal region. We used Western blotting, quantitative RT-PCR, immunofluorescence, immunohistochemistry and Masson’s trichrome staining to explore the function of S100A4. Results: We found significant increases of S100A4 level and cardiac fibrosis markers, and β-catenin signaling activation in vitro and in vivo. In addition, knockdown of S100A4 significantly reduced cardiac fibrosis and β-catenin levels. Moreover, the expression of S100A4 decreased after ICG-001 inhibited β-catenin signal pathway. Conclusion: Downregulation of S100A4 alleviates cardiac fibrosis via Wnt/β -catenin pathway in mice. S100A4 may be a therapeutic target of cardiac fibrosis.