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Significance In the context of myofibroblast–fibroblast interaction during fibrosis expansion, the mechanistic insights of intercellular mechanical communication have been poorly evidenced. We systematically investigated the myofibroblast–fibroblast cross talk via the fibrous matrix, which we termed “paratensile signaling” in the context of fibrosis expansion. We experimentally investigated and mathematically modeled the spatiotemporal features of paratensile signaling and revealed the related molecular mechanisms. We showed that paratensile signaling contributes to fibrosis progression and blocking it might potentially attenuate fibrosis expansion. Our comprehensive investigation of paratensile signaling in fibrosis expansion will broaden the understanding of the cellular dynamics during fibrogenesis and inspire paratensile-targeting antifibrotic intervention strategies.

Matrix-transmitted paratensile signaling enables myofibroblast – fibroblast cross talk in fibrosis expansion