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

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-03-07 DOI:10.1016/j.isci.2025.112176

Tomohiro Nakata , Yuhei Kirita , Minato Umehara , Masashi Nakamura , Shinji Sawai , Atsushi Minamida , Hiroko Yamauchi-Sawada , Yasuto Sunahara , Yayoi Matoba , Natsuko Okuno-Ozeki , Itaru Nakamura , Kunihiro Nakai , Aya Yagi-Tomita , Noriyuki Yamashita , Keiichi Tamagaki , Benjamin D. Humphreys , Satoaki Matoba , Tetsuro Kusaba

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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 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-extracellular signal-regulated kinase (ERK) signaling. In vivo analyses utilizing tubular-specific CCN1 knockout (KO) mice demonstrated the sparse accumulation of fibroblasts around injured sites after injury, resulting in ameliorated tissue fibrosis 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 time points.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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