title: Inhibitory effects of C-type natriuretic peptide on the differentiation of cardiac fibroblasts, and secretion of monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1.
abstract: The present study aimed to investigate the effect of C-type natriuretic peptide (CNP) on the function of cardiac fibroblasts (CFs). Western blotting was used to investigate the expression of myofibroblast marker proteins: α-smooth muscle actin (α-SMA), extra domain-A fibronectin, collagen I and collagen III, and the activity of extracellular signal-regulated kinase 1/2 (ERK1/2). Immunofluorescence was used to examine the morphological changes; a transwell assay was used to analyze migration, and reverse transcription-quantitative polymerase chain reaction and ELISA were employed to determine the mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1). The results demonstrated that CNP significantly reduced the protein expression of α-SMA, fibronectin, collagen I and collagen III, and suppressed the migratory ability of CFs. Additionally, the mRNA and protein expression of MCP-1 and PAI-1 was inhibited under the CNP treatment; and this effect was mediated by the inhibition of the ERK1/2 activity. In conclusion, CNP inhibited cardiac fibroblast differentiation and migration, and reduced the secretion of MCP-1 and PAI-1, which demonstrates novel mechanisms to explain the antifibrotic effect of CNP.
authors.affiliation: Department of Pediatric Cardiac Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: Department of Pediatric Cardiac Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Ying-Long
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Pediatric Cardiac Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pediatric Cardiac Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pediatric Cardiac Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatric Cardiac Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: Department of Pediatric Cardiac Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats
chemical_list: D018932:Chemokine CCL2; D017395:Plasminogen Activator Inhibitor 1; D020098:Natriuretic Peptide, C-Type; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3