Abstract The liver represents a site of expression of neurotrophins and their receptors. We have characterized the expression and intracellular localization of the nerve growth factor (NGF) receptor, Trk-A, in liver cells in vivo and in vitro. In both normal and fibrotic liver tissue, Trk-A immunostaining was present in different cell types, including parenchymal cells and cells of the inflammatory infiltrate. In hepatocytes and activated stellate cells (HSC), Trk-A showed a predominant nuclear localization, both in the presence and absence of injury. In cultured HSC, Trk-A was found to be functional, because exposure of the cells to recombinant NGF resulted in stimulation of cell migration and activation of intracellular signaling pathways, including Ras-ERK and PI3K/Akt. Remarkably, in cultured HSC, Trk-A staining was found constitutively in the nucleus. In these cells, Trk-A could be stained only by antibodies directed against the intracellular domain but not by those recognizing the extracellular portion of Trk-A suggesting that the intracellular portion of the receptor is the major determinant of nuclear Trk-A staining. In contrast to HSC, freshly isolated hepatocytes did not show any nuclear localization of the intracellular portion of Trk-A. In pheocromocytoma cells, nuclear staining for Trk-A was not present in conditions of serum deprivation, but could be induced by exposure to NGF or to a mixture of soluble mediators. We conclude that nuclear localization of the intracellular domain of Trk-A is observed constitutively in liver cells such as HSC, while in other cell types it could be induced in response to soluble factors.

Nuclear localization of TRK-A in liver cells / A. BONACCHI; ML TADDEI ; I PETRAI ;E EFSEN ; R. DEFRANCO ; D. NOSI ; M. TORCIA; P. ROSINI ; L. FORMIGLI ; K. ROMBOUTS ; S. ZECCHI; S. MILANI ; M. PINZANI ; G. LAFFI ; F. MARRA. - In: HISTOLOGY AND HISTOPATHOLOGY. - ISSN 0213-3911. - ELETTRONICO. - 23:(2008), pp. 327-340.

Nuclear localization of TRK-A in liver cells.

TADDEI, MARIA LETIZIA;NOSI, DANIELE;TORCIA, MARIA;FORMIGLI, LUCIA;ROMBOUTS, KRISTA LOUISA PIETER;ZECCHI, SANDRA;MILANI, STEFANO;PINZANI, MASSIMO;LAFFI, GIACOMO;MARRA, FABIO
2008

Abstract

Abstract The liver represents a site of expression of neurotrophins and their receptors. We have characterized the expression and intracellular localization of the nerve growth factor (NGF) receptor, Trk-A, in liver cells in vivo and in vitro. In both normal and fibrotic liver tissue, Trk-A immunostaining was present in different cell types, including parenchymal cells and cells of the inflammatory infiltrate. In hepatocytes and activated stellate cells (HSC), Trk-A showed a predominant nuclear localization, both in the presence and absence of injury. In cultured HSC, Trk-A was found to be functional, because exposure of the cells to recombinant NGF resulted in stimulation of cell migration and activation of intracellular signaling pathways, including Ras-ERK and PI3K/Akt. Remarkably, in cultured HSC, Trk-A staining was found constitutively in the nucleus. In these cells, Trk-A could be stained only by antibodies directed against the intracellular domain but not by those recognizing the extracellular portion of Trk-A suggesting that the intracellular portion of the receptor is the major determinant of nuclear Trk-A staining. In contrast to HSC, freshly isolated hepatocytes did not show any nuclear localization of the intracellular portion of Trk-A. In pheocromocytoma cells, nuclear staining for Trk-A was not present in conditions of serum deprivation, but could be induced by exposure to NGF or to a mixture of soluble mediators. We conclude that nuclear localization of the intracellular domain of Trk-A is observed constitutively in liver cells such as HSC, while in other cell types it could be induced in response to soluble factors.
2008
23
327
340
A. BONACCHI; ML TADDEI ; I PETRAI ;E EFSEN ; R. DEFRANCO ; D. NOSI ; M. TORCIA; P. ROSINI ; L. FORMIGLI ; K. ROMBOUTS ; S. ZECCHI; S. MILANI ; M. PINZANI ; G. LAFFI ; F. MARRA
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/257410
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