FGF10Signaling Enhances Epicardial Cell Expansion during Neonatal Mouse Heart Repair.
Unlike zebrafish and newt hearts, mammalian hearts have limited capacity to regenerate. Upon injury or disease, the adult mammalian hearts form a fibrotic scar. Recently, it was shown that neonatal mouse hearts can regenerate similarly to adult zebrafish hearts. However, this capacity quickly decreases after postnatal day 7 (P7). Understanding the molecular mechanisms underlying neonatal heart regeneration might lead to therapeutic approaches for regenerating adult mammalian hearts. In this study, we utilized an inducible transgenic mouse model to determine the effects of FGF10 growth factor over expression on neonatal mouse heart regeneration/repair. Over expression of FGF10 in myocardium enhanced the expansion of Wt1 positive epicardial cells at 21 days after heart injury through increased proliferation. However, this expansion of epicardial cells did not lead to increased epithelial-to-mesenchymal transition or affect fibroblast formation or fibrosis, as seen by vimentin expression, after heart injury. Furthermore, neither continuous nor transient expression of FGF10 did not affect scar thickness or length after heart injury in neonatal hearts. Our results suggest that FGF10 can regulate epicardial cell expansion of neonatal mouse hearts after injury; however, FGF10 alone is not sufficient to cause beneficial effects on heart repair.
Heart Institute and Program of Developmental Biology and Regenerative Medicine, USA ; The Saban Research Institute of Children's Hospital Los Angeles, USA ; Department of Pathology, Keck School of Medicine, University of Southern California, USA.
Nicole
N
Rubin
Heart Institute and Program of Developmental Biology and Regenerative Medicine, USA ; The Saban Research Institute of Children's Hospital Los Angeles, USA.
Ali
A
Darehzereshki
Department of Internal Medicine II, University of Giessen Lung Center, Giessen, Germany.
Saverio
S
Bellusci
Department of Biological and Materials Sciences, University of Michigan, Ann Arbor, Michigan, USA.
Vesa
V
Kaartinen
Heart Institute and Program of Developmental Biology and Regenerative Medicine, USA ; The Saban Research Institute of Children's Hospital Los Angeles, USA ; Department of Surgery, Keck School of Medicine, University of Southern California, USA ; Department of Biochemistry and Molecular Biology, University of Southern California, USA.
Ching
C
Ling Lien
Cardiomyocytes; Hypoplasia; Mesenchymal transition