title: Genetic Deletion of the Stromal Cell Marker CD248 (Endosialin) Protects against the Development of Renal Fibrosis.
abstract: BACKGROUND
  Tissue fibrosis and microvascular rarefaction are hallmarks of progressive renal disease. CD248 is a transmembrane glycoprotein expressed by key effector cells within the stroma of fibrotic kidneys including pericytes, myofibroblasts and stromal fibroblasts. In human disease, increased expression of CD248 by stromal cells predicts progression to end-stage renal failure. We therefore, hypothesized that the genetic deletion of the CD248 gene would protect against fibrosis following kidney injury.
  
  
  METHODS
  Using the unilateral ureteral obstruction (UUO) model of renal fibrosis, we investigated the effect of genetic deletion of CD248 on post obstructive kidney fibrosis.
  
  
  RESULTS
  CD248 null mice were protected from fibrosis and microvascular rarefaction following UUO. Although the precise mechanism is not known, this may to be due to a stabilizing effect of pericytes with less migration and differentiation of pericytes toward a myofibroblast phenotype in CD248-/- mice. CD248-/- fibroblasts also proliferated less and deposited less collagen in vitro.
  
  
  CONCLUSIONS
  These studies suggest that CD248 stromal cells have a pathogenic role in renal fibrosis and that targeting CD248 is effective at inhibiting both microvascular rarefaction and renal fibrosis through modulation of pericyte and stromal cell function.
authors.affiliation: Center for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Stuart William
authors.initials: SW
authors.lastname: Smith
authors.forename: Adam Paul
authors.initials: AP
authors.lastname: Croft
authors.forename: Hannah Louise
authors.initials: HL
authors.lastname: Morris
authors.forename: Amy Jane
authors.initials: AJ
authors.lastname: Naylor
authors.forename: David Leonard
authors.initials: DL
authors.lastname: Huso
authors.forename: Clare Marie
authors.initials: CM
authors.lastname: Isacke
authors.forename: Caroline Olivia Susan
authors.initials: CO
authors.lastname: Savage
authors.forename: Christopher Dominic
authors.initials: CD
authors.lastname: Buckley
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D007668:Kidney / Q000737:chemistry / Q000473:pathology*; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020286:Pericytes / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology; D017154:Stromal Cells / Q000737:chemistry / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; D017479:Receptors, Platelet-Derived Growth Factor