title: Involvement of the renin-angiotensin system in the development of nephrogenic systemic fibrosis-like lesions in the RenTag mouse model.
abstract: BACKGROUND
  Renin-angiotensin system (RAS) activation increases angiotensin II production stimulating profibrotic factors, especially in the setting of chronic kidney disease. Nephrogenic systemic fibrosis (NSF) has been associated with gadolinium (Gd) exposure and renal failure. RAS involvement in NSF is unclear compared to transforming growth factor beta and Smad. RenTag mice were chosen to investigate the role of RAS in NSF-like dermal fibrosis because they demonstrated dermal fibrosis at birth, perturbations of RAS in subcutaneous tissue, and renal failure within 4 weeks of age.
  
  
  METHODS
  Wild-type and RenTag mice were injected weekly with a supratherapeutic dose of intravenous gadodiamide (3.0 mmol/kg body weight) and killed at 12 weeks of age for skin and kidney histology.
  
  
  RESULTS
  RenTag mice had elevated BUN levels, pitted kidneys, and glomerular damage. RenTag mice skin revealed an increased density of fibroblasts, no mucopolysaccharide deposits, and increased collagen fibril density regardless of Gd exposure. Skin and kidney histopathology of wild-type mice were normal regardless of Gd exposure. CD34 positivity was higher in RenTag compared to wild-type.
  
  
  CONCLUSIONS
  Since RenTag dermal lesions remained unchanged after gadolinium exposure in the setting of renal failure, this animal model suggests perturbations of subcutaneous RAS may be involved in Gd-naïve dermal fibrosis.
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sexton
authors.affiliation: Erie County Medical Center, State University of New York at Buffalo, 462 Grider Street, Buffalo, NY, 14215, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Tulowitzki
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Jones
authors.affiliation: Erie County Medical Center, State University of New York at Buffalo, 462 Grider Street, Buffalo, NY, 14215, USA.
authors.forename: Silvi
authors.initials: S
authors.lastname: Shah
authors.affiliation: Erie County Medical Center, State University of New York at Buffalo, 462 Grider Street, Buffalo, NY, 14215, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hajduczok
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Gross
authors.affiliation: Erie County Medical Center, State University of New York at Buffalo, 462 Grider Street, Buffalo, NY, 14215, USA. mpanesar@ecmc.edu.
authors.forename: Mandip
authors.initials: M
authors.lastname: Panesar
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007668:Kidney / Q000473:pathology*; D008822:Mice, Transgenic; D054989:Nephrogenic Fibrosing Dermopathy / Q000473:pathology; D012084:Renin-Angiotensin System
keywords: Animal model; Gadolinium; Nephrogenic systemic fibrosis; Renin; Renin–angiotensin system; Transgenic