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Injured tubular epithelia-derived CCN1 promotes the mobilization of fibroblasts toward the injury sites in acute kidney injury

ABSTRACT: Humoral factors that prompt fibroblasts to migrate to an injury site at an appropriate time point are deemed indispensable for repair after kidney injury. We herein demonstrated the pivotal roles for of injured tubule-derived Cellular Communication Network Factor 1 (CCN1) in the mobilization of fibroblasts to the injury site after kidney injury. Based on analyses of ligand-receptor interactions in vitro and tubular epithelial-specific transcriptomics in vivo, we identified the up-regulation of CCN1 during the early phases of kidney injury. CCN1 promotes fibroblast chemotaxis through focal adhesion kinase-ERK signaling. In vivo analyses utilizing tubular-specific CCN1 knockout mice demonstrated the sparse accumulation of fibroblasts around injured sites after injury, resulting that tissue fibrosis was ameliorated in CCN1-KO mice. These results reveal an epithelial - fibroblast CCN1 signaling axis that mobilizes fibroblasts to injured tubule early after acute injury but that promotes interstitial fibrosis at late timepoints.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE248209 | GEO | 2025/03/03

REPOSITORIES: GEO

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Injured tubular epithelia-derived CCN1 promotes the mobilization of fibroblasts toward the injury sites in acute kidney injury

Project description:Injured tubular epithelia-derived CCN1 promotes the mobilization of fibroblasts toward the injury sites in acute kidney injury

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