title: Nerve growth factor exposure promotes tubular epithelial-mesenchymal transition via TGF-β1 signaling activation.
abstract: Clinical studies showed that renal expression and serum levels of nerve growth factor (NGF) are increased in renal diseases characterized by progressive fibrosis, a pathologic process in which TGF-β1 mediates most of the key events leading to tubular epithelial-mesenchymal transition (EMT). However, the pathogenic role of high NGF levels has not yet been elucidated. In this study, we found that in tubular renal cells, HK-2, NGF transcriptionally up-regulated TGF-β1 expression and secretion and enhanced cell motility by activating EMT markers via its receptors, TrkA and p75(NTR). Interestingly, we observed that TGF-β1-SMAD pathway activation and the up-regulation of EMT markers NGF-induced were both prevented when knockdown of TGF-β1 gene occurred and that the pretreatment with an antibody anti-NGF reversed the nuclear translocation of pSMAD3/SMAD4 complex. Collectively, our results demonstrated that NGF promotes renal fibrosis via TGF-β1-signaling activation, suggesting that in kidney diseases high NGF serum levels could contribute to worsen renal fibrosis.
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Vizza
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Perri
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Toteda
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Lupinacci
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Leone
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gigliotti
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Lofaro
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: La Russa
authors.affiliation: a Department of Nephrology Dialysis and Transplantation, Research Center Kidney and Transplantation , Annunziata Hospital , Cosenza , Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Bonofiglio
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005355:Fibrosis / Q000473:pathology*; D006801:Humans; D007684:Kidney Tubules / Q000502:physiology*; D020932:Nerve Growth Factor / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000473:pathology*; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051901:Smad4 Protein / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000906:Antibodies; C502240:NGF protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D017475:Receptors, Nerve Growth Factor; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1; D020932:Nerve Growth Factor; D020917:Receptor, trkA
keywords: Epithelial–mesenchymal transition; TGF-β1; nerve growth factor; renal fibrosis; tubular renal cells