Protein kinase C promotes cardiac fibrosis and heart failure by modulating galectin-3 expression

• Published in: Biochimica et biophysica acta Vol. 1853; no. 2; pp. 513 - 521
• Main Authors: Song, Xiang, Qian, Xiaoqian, Shen, Ming, Jiang, Rong, Wagner, Mary B., Ding, Guoliang, Chen, Guangping, Shen, Baozhong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2015
• Subjects: Angiotensin II; Angiotensin II - pharmacology; Animals; Cardiac fibrosis; Cell Line; Collagen; Collagen Type I - metabolism; Enzyme Activation; Fibronectins - metabolism; Fibrosis; Galectin 3 - metabolism; Heart failure; Heart Failure - diagnostic imaging; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - physiopathology; Male; Mice; Myocardium - metabolism; Myocardium - pathology; Protein kinase; Protein Kinase C - metabolism; Pulmonary Artery - drug effects; Pulmonary Artery - pathology; Rats, Sprague-Dawley; Ultrasonography; Heart failure; Cardiac fibrosis; Angiotensin II; Protein kinase; Collagen
• DOI: 10.1016/j.bbamcr.2014.12.001
• EISSN: 1879-2596
• ISSN: 0167-4889; 0006-3002

Protein kinase C (PKC) and galectin-3 are two important mediators that play a key pathogenic role in cardiac hypertrophy and heart failure (HF). However, the molecular mechanisms and signaling pathways are not fully understood. In this study, we explored the relationship between and roles of PKC-α and galectin-3 in the development of HF. We found that activation of PKC by phorbol dibutyrate (PDB) increased galectin-3 expression by ~180%, as well as collagen I and fibronection accumulation in cultured HL-1 cardiomyocytes. Over-expression of galectin-3 in HL-1 cells increased collagen I protein production. Inhibition of galectin-3 by β-lactose blocked PDB-induced galectin-3 and collagen production, indicating that galectin-3 mediates PKC-induced cardiac fibrosis. In rats subjected to pulmonary artery banding (PAB) to induce right ventricular HF, galectin-3 was increased by ~140% in the right ventricle and also by ~240% in left ventricle compared to control. The elevated galectin-3 is consistent with an increase of total and activated (phosphorylated) PKC-α, α-SMA and collagen I. Finally, we extended our findings to examine the role of angiotensin II (Ang II), which activates the PKC pathway and contributes to cardiac fibrosis and the development of HF. We found that Ang II activated the PKC-α pathway and increased galectin-3 expression and collagen production. This study provides a new insight into the molecular mechanisms of HF mediated by PKC-α and galectin-3. PKC-α promotes cardiac fibrosis and HF by stimulation of galectin-3 expression.
•We examined the signaling pathway for PKC-α in heart failure.•Activation of the PKC pathway stimulates galectin-3 expression.•Inhibition of galectin-3 blocks PKC-stimulated collagen production.•Both PKC-α and galectin-3 are upregulated in experimental heart failure.•Angiotensin II by activation of the PKC pathway promotes galectin-3 expression.