Expression and functional interaction of hepatocyte growth factor-scatter factor and its receptor c-met in mammalian brain.

Abstract

Abstract. Hepatocyte growth factor-scatter factor (HGF-SF) is a pleiotropic cytokine with mito-, morpho-, and motogenic effects on a variety of epithelial and endothelial cells. HGF-SF activity is mediated by the c-met protooncogene, a membrane-bound tyrosine kinase. Here, we demonstrate that both genes are expressed in developing and adult mammalian brains. HGF-SF mRNA is localized in neurons, primarily in the hippocampus, the cortex, and the granule cell layer of the cerebellum, and it is also present at high levels in ependymal cells, the chorioid plexus, and the pineal body. c-met is expressed in neurons, preferentially in the CAd area of the hippocampus, the cortex, and the septum, as well as in the pons. In the embryonic mouse, brain HGF-SF and c-met are expressed as early as days 12 and 13, respectively. Neuronal expression of HGF-SF is evolutionary highly conserved and detectable beyond the mammalian class. Incubation of septal neurons in culture with HGF-SF leads to a rapid increase of c-fos mRNA levels.The results demonstrate the presence of a novel growth factor-tyrosine kinase signaling system in the brain, and they suggest that HGF-SF induces a functional response in a neuronal subpopulation of developing and adult CNS.

Hepatocyte growth factor as an enhancer of nmda currents and synaptic plasticity in the hippocampus

“…This staining in the somata may reflect an uneven level of c-Met expression among pyramidal cells. These patterns of c-Met ex-pression are mostly consistent with previous reports using a polyclonal antibody (Korhonen et al, 2000) and in situ hybridization (Jung et al, 1994). When the localization was further analyzed in dissociated neurons of the hippocampus, positive signals for c-Met were observed in neurites that were also positive for MAP-2, a marker for neuronal dendrites (Fig.…”

“…In situ hybridization (Honda et al, 1995;Jung et al, 1994) and immunohistochemical (Korhonen et al, 2000) studies have indicated that the hippocampus is a prominent site for the expressions of HGF and c-Met in the adult CNS. Here, we confirmed that c-Met protein was localized in hippocampal neurons in adult brain, where it showed a relatively high degree of Tyr-phosphorylation.…”

Hepatocyte growth factor and c-Met promote dendritic maturation during hippocampal neuron differentiation via the Akt pathway

“…Although many signals have been identified that modulate dendrite growth and maturation, relatively few have been identified that regulate the initial stages of dendrite elongation [34]. HGF and c-Met are expressed by specific classes of neurons from cerebral cortex, hippocampus, amygdala, and septum as well as by non-neuronal cells [35][36][37]. HGF initiates multiple intracellular signals to regulate protein expression, cytoskeletal rearrangement and motility, and intercellular adhesion in CNS neurons [12,38,39].…”

Transcriptional regulation of the hepatocyte growth factor (HGF) gene by the Sp family of transcription factors

“…Unlike Sp1, Sp2 and Sp3 which are ubiquitously expressed in various tissues and cell types, Sp4 is known to be brain-speci®c (Kingsley and Winoto, 1991;Fischer et al, 1993;Hagen et al, 1992). Thus Sp4 may activate HGF expression in the central nervous system since the HGF gene is also expressed in this tissue (Jung et al, 1994).…”