Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors

The expression of neurotrophins and neurotrophin receptors in non-neural ti ssue is related to tissue remodeling, differentiation, proliferation and mi gration of target cells. The literature yields contradictory results on neu rotrophin and neurotrophin receptor expression in the liver. We show immuno reactivity to antibodies to nerve growth factor (NGF), brain-derived neurot rophin (BDNF), neurotrophin 3 (NT-3), neurotrophin 4/5 (NT-4/5), the low-af finity nerve growth factor receptor p75 and the high-affinity tyrosine kina se receptors (Trk) B and C in hepatic stellate cells and weak reactivity fo r BDNF, NT-3, and NT-4/5 in hepatocytes, in cryosections of human and rat l iver, in normal and varying pathologic conditions. Immunoreactivity is uneq uivocally localized to hepatic stellate cells by double staining with alpha -smooth muscle actin (alpha -SMA) and desmin, studied by confocal laser sc anning microscopy. Finally, the presence of mRNA transcripts for the differ ent neurotrophins and neurotrophin receptors, with the exception of Trk-B, is shown by reverse transcription polymerase chain reaction (RT-PCR) on RNA extracted from freshly isolated rat hepatic stellate cells, compared with hepatocyte RNA. Hepatocyte RNA was found to contain BDNF, NT-3, NT-4/5 mRNA (which is compatible with the immunohistochemical findings) and Trk-A mRNA . In conclusion, hepatic stellate cells are a source of several neurotrophi ns in the liver and they express neurotrophin receptors. These findings cor respond with the known involvement of hepatic stellate cells in tissue remo deling, their production of extracellular matrix components and their proli feration in acute necrotizing liver pathology. In analogy with findings in other organs and systems, neurotrophins are hypothesized to play a role in the pathophysiology of liver disease.