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

Abstract：

:While the concept of intercellular mechanical communication has been revealed, the mechanistic insights have been poorly evidenced in the context of myofibroblast-fibroblast interaction during fibrosis expansion. Here we report and systematically investigate the mechanical force-mediated myofibroblast-fibroblast cross talk via the fibrous matrix, which we termed paratensile signaling. Paratensile signaling enables instantaneous and long-range mechanotransduction via collagen fibers (less than 1 s over 70 μm) to activate a single fibroblast, which is intracellularly mediated by DDR2 and integrin signaling pathways in a calcium-dependent manner through the mechanosensitive Piezo1 ion channel. By correlating in vitro fibroblast foci growth models with mathematical modeling, we demonstrate that the single-cell-level spatiotemporal feature of paratensile signaling can be applied to elucidate the tissue-level fibrosis expansion and that blocking paratensile signaling can effectively attenuate the fibroblast to myofibroblast transition at the border of fibrotic and normal tissue. Our comprehensive investigation of paratensile signaling in fibrosis expansion broadens the understanding of cellular dynamics during fibrogenesis and inspires antifibrotic intervention strategies targeting paratensile signaling.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Liu L,Yu H,Zhao H,Wu Z,Long Y,Zhang J,Yan X,You Z,Zhou L,Xia T,Shi Y,Xiao B,Wang Y,Huang C,Du Y

doi

10.1073/pnas.1910650117

subject

Has Abstract

pub_date

2020-05-19 00:00:00

pages

10832-10838

issue

20

eissn

0027-8424

issn

1091-6490

pii

1910650117

journal_volume

117

pub_type

杂志文章

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