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Pericyte Cd248 Promotes Fibrosis Through Induction Of Pro‐Fibrotic Macrophages During Kidney Injury
Author(s) -
Pai ChenHsueh,
Tsai YuFei,
Yen ChingTzu,
Lin ShuRung,
Lin ShueiLiong,
Lin ShuWha
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.816.8
Subject(s) - myofibroblast , fibrosis , pathology , downregulation and upregulation , kidney , biology , cancer research , medicine , endocrinology , biochemistry , gene
CD248, also known as endosialin or tumor endothelial marker 1, is a type I transmembrane glycoprotein that is expressed in stromal cells of normal kidneys and uterus after birth. Using lacZ knock‐in (KI/+) mice we have shown that Cd248 expression decreases in most organs but increases and persists in postnatal kidneys, specifically in glomerular mesangial cells and pericytes/perivascular fibroblasts. In human chronic kidney disease, upregulated expression of CD248 is shown in myofibroblasts, which is negatively associated with renal survival. Although limited experimental data suggest that CD248 is involved in the cross‐talk with the post‐receptor signalling and cell proliferation of fibroblasts activated by platelet‐derived growth factors, the role of CD248 in kidney fibrosis is still unclear. Many studies including ours have identified CD248 + pericytes as the major source of precursors of scar‐producing myofibroblasts during progressive kidney fibrosis. Our data showed that expression of Cd248 was upregulated in the fibrotic kidney myofibroblasts of mouse model induced by unilateral ureteral obstruction (UUO). Cd248 knockout mice ( Cd248 −/− ) showed less fibrosis and cell numbers of macrophages in the UUO kidneys. Moreover, UUO kidney macrophages expressed lower levels of chemokinde ( C‐C motif ) ligand 17 ( Ccl17 ) and Ccl22 in Cd248 −/− mice, suggesting CD248 deficiency led to a decrease of pro‐fibrotic macrophages. In vitro functional polarization assay of macrophages induced by co‐culture with wild‐type or CD248‐deficient myofibroblasts confirmed that CD248 played a role in the differentiation of pro‐fibrotic macrophages. Our results suggest that pericyte CD248 promotes fibrosis through induction of pro‐fibrotic macrophages during kidney injury. Support or Funding Information This study is supported by MOST (105‐2314‐B‐002 ‐096 ‐MY3 and 106‐2319‐B‐002‐001) and the Mrs. Hsiu‐Chin Lee Kidney Research Foundation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .