title: Translational study of the Notch pathway in hypertensive nephropathy.
abstract: BACKGROUND
  The Notch signalling pathway is activated in a wide variety of human renal diseases. We have recently demonstrated that the activation of this pathway is not involved in experimental renal fibrosis induced by angiotensin II or hypertension.
  
  
  OBJECTIVE
  To assess whether the Notch pathway is activated in renal fibrosis related to hypertensive nephrosclerosis. To test the hypothesis, various glomerular diseases characterised by tubulointerstitial fibrosis were analysed.
  
  
  METHODS
  Renal biopsies were performed on patients with hypertensive nephrosclerosis, in comparison with diabetic nephropathy and membranous nephropathy at various stages. Gene and protein expression were evaluated by in-situ hybridisation and immunohistochemistry respectively.
  
  
  RESULTS
  In hypertensive nephrosclerosis low renal expression of notch-related proteins was observed. There was no link between tubulointerstitial fibrosis and the levels of these proteins. By contrast, in the glomerular diseases studied we observed high expression of the transcripts Jagged-1, HES-1 and TGF-β and the proteins Jagged-1 y Notch-1, localised primarily in tubuloepithelial cells. The levels of expression of the components of the Notch pathway correlate to the degree of tubulointerstitial fibrosis, which confirms the activation of this pathway in progressive nephropathies.
  
  
  CONCLUSIONS
  Our data demonstrate that the Notch pathway is not activated in the kidneys of patients with hypertensive nephropathy, which extends the results of experimental models of kidney damage related to hypertension to the realm of human pathology. Our studies provide new information on the complex regulation of the Notch pathway in the kidney.
authors.forename: Carolina
authors.initials: C
authors.lastname: Lavoz
authors.forename: Alejandra
authors.initials: A
authors.lastname: Droguett
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Burgos
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Carpio
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Sergio
authors.initials: S
authors.lastname: Mezzano
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
mesh_terms: D005260:Female; D005355:Fibrosis / Q000503:physiopathology; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000235:genetics / Q000503:physiopathology*; D014176:Protein Biosynthesis; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology*; D012189:Retrospective Studies; D015398:Signal Transduction
chemical_list: D051880:Receptors, Notch