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

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.

• Authors: Mateusz S Wietecha, Marco Pensalfini, Michael Cangkrama, Bettina Müller, Juyoung Jin, Jürgen Brinckmann, Edoardo Mazza, Sabine Werner
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 2604 (05 25 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 32451392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• inhibin beta A subunit
• Collagen
• Inhibin-beta Subunits

Topics

• Animals
• Biomechanical Phenomena
• Cell Line
• Cicatrix (pathology, physiopathology)
• Cicatrix, Hypertrophic (pathology, physiopathology)
• Collagen (metabolism)
• Extracellular Matrix (genetics, metabolism)
• Female
• Fibroblasts (metabolism)
• Fibrosis
• Humans
• Inhibin-beta Subunits (genetics, metabolism)
• Keratinocytes (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Skin (injuries, metabolism, pathology)
• Transcriptome
• Up-Regulation
• Wound Healing (genetics, physiology)