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

First Author  Wietecha MS Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  2604
PubMed ID  32451392 Mgi Jnum  J:292052
Mgi Id  MGI:6447098 Doi  10.1038/s41467-020-16409-z
Citation  Wietecha MS, et al. (2020) Activin-mediated alterations of the fibroblast transcriptome and matrisome control the biomechanical properties of skin wounds. Nat Commun 11(1):2604
abstractText  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.
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