Identification of a myofibroblast-specific expression signature in skin wounds
Abstract
After skin injury fibroblasts migrate into the wound and transform into contractile, extracellular matrix-producing myofibroblasts to promote skin repair. Persistent activation of myofibroblasts can cause excessive fibrotic reactions, but the underlying mechanisms are not fully understood. We used SMA-GFP transgenic mice to study myofibroblast recruitment and activation in skin wounds. Myofibroblasts were initially recruited to wounds three days post injury, their number reached a maximum after seven days and subsequently declined. Expression profiling showed that 1749 genes were differentially expressed in sorted myofibroblasts from wounds seven days post injury. Most of these genes were linked with the extracellular region and cell periphery including genes encoding for extracellular matrix proteins. A unique panel of core matrisome and matrisome-associated genes was differentially expressed in myofibroblasts and several genes not yet known to be linked to myofibroblast-mediated wound healing were found (e.g. Col24a1, Podnl1, Bvcan, Tinagl1, Thbs3, Adamts16, Adamts19, Cxcl's, Ccl's). In addition, a complex network of G protein-coupled signaling events was regulated in myofibroblasts (e.g. Adcy1, Plbc4, Gnas). Hence, this first characterization of a myofibroblast-specific expression profile at the peak of in situ granulation tissue formation provides important insights into novel target genes that may control excessive ECM deposition during fibrotic reactions.
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Fibroblasts are capable of remarkable plasticity and phenotype switching during progression and regression of fibrosis.
“Fibroblasts, in addition to displaying significant functional heterogeneity, are capable of remarkable degrees of plasticity and phenotype switching during progression and regression of fibrosis30,35,36.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [35]
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Fibrosis: from mechanisms to medicines
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020) · Nature · doi:10.1038/s41586-020-2938-9 · Cited by 1,868 · see citing works
- Authors
- Bergmeier, V., Etich, J., Pitzler, L., Frie, C., Koch, M., Fischer, M., Rappl, G., Abken, H., Tomasek, J. J., & Brachvogel, B.
- Affiliations
- University of Cologne (DE)
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Brachvogel, Bent
- ORCID
- Venue
- Matrix Biology
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 65
- Pages
- 59-74
- ISSN
- 0945-053X (ISSN-L)
- OpenAlex
- W2742741708
- Cited by
- 87
- References
- 65
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 21 · 2023: 10 · 2022: 16 · 2021: 10 · 2020: 10 · 2019: 5 · 2018: 4
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Matrix Biology (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Funders
- Bladder Cancer Advocacy Network
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- myofibroblasts, skin wound healing, gene expression signatures, extracellular matrix, matrisome, fibrosis, granulation tissue, fibroblast recruitment, G protein-coupled receptor signaling, extracellular matrix deposition
- MeSH terms
- Actins, Animals, Cell Differentiation, Disease Models, Animal, Gene Expression Regulation, Mice, Transgenic, Organ Specificity, Skin, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Gene Regulatory Networks, Myofibroblasts
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