English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

The role of fibroblasts in tissue fibrosis has been extensively studied. Activated fibroblasts, namely myofibroblasts, produce pathological extracellular matrix. CD248, a type I transmembrane glycoprotein, is expressed in fibroblasts after birth. In human chronic kidney disease, upregulated CD248 in myofibroblasts is linked to poor renal survival. In this study, we demonstrated a novel interaction between CD248 and macrophages to be a key step in mediating tissue fibrosis. CD248 was upregulated in myofibroblasts in murine models of renal and peritoneal fibrosis.  Cd248  knockout ( Cd248   –/–  ) could attenuate both renal and peritoneal fibrosis. By parabiosis of GFP reporter mice and  Cd248   –/–   mice, we showed that attenuation of renal fibrosis was associated with a decrease of macrophage infiltration in  Cd248   –/–   mice. Moreover, decrease of  chemokine  ( C–C motif )  ligand 17  and  Ccl22  was found in macrophages isolated from the fibrotic kidneys of  Cd248   –/–   mice. Because galectin-3-deficient macrophages showed decreased  Ccl17  and  Ccl22  in fibrotic kidneys, we further demonstrated that CD248 interacted specifically with galectin-3 of macrophages who then expressed CCL17 to activate collagen production in myofibroblasts. Mice with DNA vaccination targeting CD248 showed decreased fibrosis. We thus propose that CD248 targeting should be studied in the clinical tissue fibrosis setting.

Targeting fibroblast CD248 attenuates CCL17-expressing macrophages and tissue fibrosis