title: Changes in renal WT-1 expression preceding hypertension development.
abstract: BACKGROUND
  Hypertension is a public health problem with mostly unknown causes, and where strong hereditary genetic alterations have not been fully elucidated. However, the use of experimental models has provided valuable information. Recent evidences suggest that alterations in key nephrogenic factors, such as Wilms' tumor 1 transcription factor (WT-1), could contribute to the development of hypertension. The aim of this paper is to evaluate the expression of WT-1 and related genes in the nephrogenic process in connection with the development of hypertension as well as the corresponding anatomical and functional correlation.
  
  
  METHODS
  Male spontaneously hypertensive and control rats were evaluated weekly from birth until week 8 of life. Their blood pressure was taken weekly using the tail-cuff blood pressure system. Weekly, 5 rats per group were sacrificed with a lethal injection of pentobarbital, and their kidneys were removed, decapsulated and weighed. The serum was collected for measuring biochemical parameters. The results were assessed using one-way analysis of variance for comparisons between groups.
  
  
  RESULTS
  The relationship between renal weight/total body weights was established, without significantly different values. These data were compared with apoptosis, fibrosis, number and size of the glomeruli. The elevation of systolic blood pressure was significant since week 6. Biochemical values differed slightly. Histology showed a slight increase in deposits of collagen fibers since week 4. Additionally, in kidney cortices, the expression of WT-1, heat shock protein 70 (Hsp70) and vitamin D receptors (VDR) decreased since week 4. Finally, we demonstrated ultrastructural damage to mitochondria since week 4.
  
  
  CONCLUSIONS
  Our results would suggest an unprecedented link, possibly a regulatory mechanism, between WT-1 on nephrogenic alteration processes and their relationship with hypertension. Moreover, and previous to the increase in blood pressure, we demonstrated low expressions of WT-1, VDR and Hsp70 in kidneys from neonatal SHRs. If so, this may suggest that deregulation in the expression of WT-1 and its impact on nephrogenesis induction could be crucial in understanding the development and maintenance of hypertension.
authors.affiliation: National Scientific and Technical Research Council, Institute of Medical and Experimental Biology of Cuyo, Mendoza, Argentina.|Pathology Department, Pharmacology Area Medical Sciences College, National University of Cuyo, Mendoza, CP5500, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Mazzei
authors.affiliation: Pathology Department, Pharmacology Area Medical Sciences College, National University of Cuyo, Mendoza, CP5500, Argentina.
authors.forename: Mercedes
authors.initials: M
authors.lastname: García
authors.affiliation: Pathology Department, Pharmacology Area Medical Sciences College, National University of Cuyo, Mendoza, CP5500, Argentina.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Calvo
authors.affiliation: Pathology Department, Pharmacology Area Medical Sciences College, National University of Cuyo, Mendoza, CP5500, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Casarotto
authors.affiliation: National Scientific and Technical Research Council, Institute of Histology and Embryology of Mendoza, Mendoza, Argentina.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fornés
authors.affiliation: Pathology Department, Pharmacology Area Medical Sciences College, National University of Cuyo, Mendoza, CP5500, Argentina.
authors.forename: María Angélica
authors.initials: MA
authors.lastname: Abud
authors.affiliation: National Scientific and Technical Research Council, Institute of Medical and Experimental Biology of Cuyo, Mendoza, Argentina.
authors.forename: Darío
authors.initials: D
authors.lastname: Cuello-Carrión
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Puerto Rico University, Puerto Rico, EEUU, USA.
authors.forename: León
authors.initials: L
authors.lastname: Ferder
authors.affiliation: National Scientific and Technical Research Council, Institute of Medical and Experimental Biology of Cuyo, Mendoza, Argentina. wmanucha@yahoo.com.ar.|Pathology Department, Pharmacology Area Medical Sciences College, National University of Cuyo, Mendoza, CP5500, Argentina. wmanucha@yahoo.com.ar.
authors.forename: Walter
authors.initials: W
authors.lastname: Manucha
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001794:Blood Pressure; D001835:Body Weight; D005355:Fibrosis; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000648:ultrastructure*; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018167:Receptors, Calcitriol / Q000378:metabolism; D025721:WT1 Proteins / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018167:Receptors, Calcitriol; D025721:WT1 Proteins
keywords: Heat shock protein 70; Hypertension; Mitochondria; Nephrogenesis; Vitamin D receptor; Wilms’ tumor 1 factors