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

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Genetic Deletion of the Stromal Cell Marker CD248 (Endosialin) Protects against the Development of Renal Fibrosis. / Smith, Stuart; Croft, Adam; Morris, Hannah Louise; Naylor, Amy; Huso, David Leonard; Isacke, Claire Marie; Savage, Caroline; Buckley, Christopher.

In: Nephron, Vol. 131, No. 4, 04.12.2015.

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@article{d0be4053f9544a3394bb24a2a29b282c,
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. 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.",
keywords = "CD248, Endosialin, Fibrosis, Kidney",
author = "Stuart Smith and Adam Croft and Morris, {Hannah Louise} and Amy Naylor and Huso, {David Leonard} and Isacke, {Claire Marie} and Caroline Savage and Christopher Buckley",
year = "2015",
month = "12",
day = "4",
doi = "10.1159/000438754",
language = "English",
volume = "131",
journal = "Nephron",
issn = "0028-2766",
publisher = "Karger",
number = "4",

}

RIS

TY - JOUR

T1 - Genetic Deletion of the Stromal Cell Marker CD248 (Endosialin) Protects against the Development of Renal Fibrosis

AU - Smith, Stuart

AU - Croft, Adam

AU - Morris, Hannah Louise

AU - Naylor, Amy

AU - Huso, David Leonard

AU - Isacke, Claire Marie

AU - Savage, Caroline

AU - Buckley, Christopher

PY - 2015/12/4

Y1 - 2015/12/4

N2 - 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.

AB - 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.

KW - CD248

KW - Endosialin

KW - Fibrosis

KW - Kidney

UR - http://www.karger.com/Article/FullText/438754

U2 - 10.1159/000438754

DO - 10.1159/000438754

M3 - Article

C2 - 26633297

VL - 131

JO - Nephron

JF - Nephron

SN - 0028-2766

IS - 4

ER -