Genetic Deletion of the Stromal Cell Marker CD248 (Endosialin) Protects against the Development of Renal Fibrosis

Research output: Contribution to journalArticle

Authors

  • Hannah Louise Morris
  • David Leonard Huso
  • Claire Marie Isacke

External organisations

  • Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.
  • Department of Molecular and Comparative Pathobiology, The Sidney Kimmel Comprehensive Cancer Center, John Hopkins Medical Institutions, Baltimore, Md.
  • Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London

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. Conclusion: 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.

Details

Original languageEnglish
JournalNephron
Volume131
Issue number4
Early online date4 Dec 2015
Publication statusE-pub ahead of print - 4 Dec 2015

Keywords

  • CD248, Endosialin, Fibrosis, Kidney