Activin-mediated alterations of the fibroblast transcriptome and matrisome control the biomechanical properties of skin wounds

Mateusz S. Wietecha, Marco Pensalfini, Michael Cangkrama, Bettina Müller, Juyoung Jin, Jürgen Brinckmann, Edoardo Mazza () and Sabine Werner ()
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Mateusz S. Wietecha: ETH Zurich
Marco Pensalfini: ETH Zurich
Michael Cangkrama: ETH Zurich
Bettina Müller: ETH Zurich
Juyoung Jin: ETH Zurich
Jürgen Brinckmann: University of Lübeck
Edoardo Mazza: ETH Zurich
Sabine Werner: ETH Zurich

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: Abstract Matrix deposition is essential for wound repair, but when excessive, leads to hypertrophic scars and fibrosis. The factors that control matrix deposition in skin wounds have only partially been identified and the consequences of matrix alterations for the mechanical properties of wounds are largely unknown. Here, we report how a single diffusible factor, activin A, affects the healing process across scales. Bioinformatics analysis of wound fibroblast transcriptome data combined with biochemical and histopathological analyses of wounds and functional in vitro studies identify that activin promotes pro-fibrotic gene expression signatures and processes, including glycoprotein and proteoglycan biosynthesis, collagen deposition, and altered collagen cross-linking. As a consequence, activin strongly reduces the wound and scar deformability, as identified by a non-invasive in vivo method for biomechanical analysis. These results provide mechanistic insight into the roles of activin in wound repair and fibrosis and identify the functional consequences of alterations in the wound matrisome at the biomechanical level.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16409-z

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DOI: 10.1038/s41467-020-16409-z

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