Hepatocyte Growth Factor and Its Receptor Are Expressed in Cardiac Myocytes During Early Cardiogenesis

Abstract

Rappolee DA, Iyer A, Patel, Y. Hepatocyte growth factor and its receptor are expressed in cardiac myocytes during early cardiogenesis. Circulation Research. 1996; 78: 1028-1036. doi:10.1161 AbstractAbstract In the mouse, the heart primordium arises when mesoderm is set aside during gastrulation, is induced by pharyngeal endoderm, migrates ventrally to the midline of the embryo, forms a tube, and begins beating. Little is known of the molecular mechanisms that mediate the determination, mitosis, differentiation, and migration that lead to the beating heart. Transcripts for hepatocyte growth factor/scatter factor (HGF) and its receptor are coexpressed transiently and dynamically in the premyocardium but not in other heart progenitor cells. Transcripts for HGF ligand and receptor are first detected before cardiac function and looping and persist through the first looping stage, when heart morphology begins to elaborate. HGF ligand and receptor mRNA are detectable after the putative heart transcription factor, Csx/Nkx2-5, and concomitantly with the heart structural gene, cardiac actin. HGF receptor mRNA is detected in the mesoderm of the headfold stage and persists in myocardial precursors of the ventricles and atria (but not in the outflow-tract smooth muscle cells) through the 14-somite stage at 8.75 days after fertilization (day E8.75). At the headfold stage, between E7.5 and E8.0, HGF receptor mRNA was detected in myocardial cells before fusion at the ventral midline. HGF ligand and receptor mRNA transcripts are coexpressed in the embryo, except in the headfold stage (when only the HGF receptor can be detected) and in the heart at the 14-to 18-somite stage (when only HGF ligand can be detected). The dynamic pattern of coexpression suggests an autoregulatory role for HGF and its receptor in early heart development.

Injured cardiomyocytes promote dental pulp mesenchymal stem cell homing

“…Likewise it also appears not involved in MUR-1 cell migration. Finally, HGF mediates the premyocardium formation through the condensation of cardiac neural crest cells, and later it contributes to drive the whole early heart development [52], whilst SDF-1 induces their condensation around the aortic arch arteries [24], whose proper development is regulated by FGF-2 [30,53]. Both HGF and SDF-1 expressions are needed to promote the cell commitment towards CM lineage via the induction of Gata4 and Mef2c transcription factors [54,55], already expressed by MUR-1 cells [17].…”

The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells

“…Actually, the myocardial synthesis of fibronectin seems to precede the arrival of the epicardial cells to the myocardium (Ká lmá n et al, 1995) and may play a role in directing epicardial migration. The subepicardium also accumulates growth factors such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) (Tomanek et al, 1998(Tomanek et al, , 1999(Tomanek et al, , 2002Zheng et al, 2001) and is likely to retain other myocardially secreted growth factors like hepatocyte growth factor (HGF) (Rappolee et al, 1996;Song et al, 1999), transforming growth factors (TGF␤s), and bone morphogenetic proteins (BMPs) (Yamagishi et al, 1999;Nakajima et al, 2000). The release of these factors appears to be partially controlled by the interactions with the matrix.…”

Cell-Based Gene Therapies and Stem Cells for Regeneration of Ischemic Tissues

“…In the selection of growth factors potentially capable to boost the regeneration of ischemic cardiovascular tissue, we and others have investigated on hepatocyte growth factor (HGF) and its receptor receptor mesenchymal-epithelial transition factor (Met). Ligand-receptor systems such HGF and its receptor, the tyrosine kinase Met, are potential candidates for therapeutic angiogenesis and for boosting migration, engraftment and commitment of CSCs because they promote the translocation of CSCs into the injured area, activate their growth and differentiation, and stimulate endothelial cell migration (Rappolee et al, 1996;Forte et al, 2006;Madonna et al, 2010). The strategy of combining stem cells, either native or gene-engineered to overexpress growth factors, with biopolymers that are functionalized with growth factors such as HGF, would facilitate myocardial regeneration: a) by supplying exogenous stem cells or GFs that stimulate resident CSC migration, engraftment and commitment to cardiomyocytes, and that induce and modulate arterial responses to ischemia; b) by supporting the maintenance of GFs and transplanted stem cells in the damaged tissues through the use of biocompatible and biodegradable polymers for a period of time sufficient to allow histological and anatomical restoration of the damaged tissue.…”