RT journal article
T1 CCBE1 Is Essential for Epicardial Function during Myocardium Development
A1 Bonet Martínez, Fernando
A1 Brito Añez, Sabrina
A1 Inácio, José M.
A1 Futschik, Matthias E.
A1 Belo, Jose A.
A2 Medicina
K1 CCBE1
K1 heart development
K1 epicardium
K1 epicardial derived cells
K1 EMT
K1 myocardial growth
AB The epicardium is a single cell layer of mesothelial cells that plays a critical role during heart development contributing to different cardiac cell types of the developing heart through epithelial-to-mesenchymal transition (EMT). Moreover, the epicardium is a source of secreted growth factors that promote myocardial growth. CCBE1 is a secreted extracellular matrix protein expressed by epicardial cells that is required for the formation of the primitive coronary plexus. However, the role of CCBE1 during epicardial development was still unknown. Here, using a Ccbe1 knockout (KO) mouse model, we observed that loss of CCBE1 leads to congenital heart defects including thinner and hyper-trabeculated ventricular myocardium. In addition, Ccbe1 mutant hearts displayed reduced proliferation of cardiomyocyte and epicardial cells. Epicardial outgrowth culture assay to assess epicardial-derived cells (EPDC) migration showed reduced invasion of the collagen gel by EPDCs in Ccbe1 KO epicardial explants. Ccbe1 KO hearts also displayed fewer nonmyocyte/nonendothelial cells intramyocardially with a reduced proliferation rate. Additionally, RNA-seq data and experimental validation by qRT-PCR showed a marked deregulation of EMT-related genes in developing Ccbe1 mutant hearts. Together, these findings indicate that the myocardium defects in Ccbe1 KO mice arise from disruption of epicardial development and function.
PB MDPI
SN 1422-0067
YR 2022
FD 2022-10
LK http://hdl.handle.net/10498/28747
UL http://hdl.handle.net/10498/28747
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 13-nov-2026