title: Protein kinase C promotes cardiac fibrosis and heart failure by modulating galectin-3 expression.
abstract: 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.
authors.affiliation: Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Qian
authors.affiliation: Center for Cardiovascular Biology, Children's Healthcare of Atlanta and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.affiliation: Center for Cardiovascular Biology, Children's Healthcare of Atlanta and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Center for Cardiovascular Biology, Children's Healthcare of Atlanta and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Wagner
authors.affiliation: Center for Cardiovascular Biology, Children's Healthcare of Atlanta and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Ding
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: gchen3@emory.edu.
authors.forename: Guangping
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Radiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: shenbzh@vip.sina.com.
authors.forename: Baozhong
authors.initials: B
authors.lastname: Shen
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D037502:Galectin 3 / Q000378:metabolism*; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D037502:Galectin 3; D000804:Angiotensin II; D011493:Protein Kinase C
keywords: Angiotensin II; Cardiac fibrosis; Collagen; Heart failure; Protein kinase