Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair
Open accessAbstract
Myofibroblast diversity with injury and aging: Fibroblasts deposit extracellular matrix (ECM) molecules to regulate tissue strength and function. However, if too much ECM is deposited, fibrosis and scarring results. Shook et al. examined cells during mouse skin wound healing, fibrosis, and aging (see the Perspective by Willenborg and Eming). They identified distinct subpopulations of myofibroblasts, including cells identified as adipocyte precursors (APs). In cellular ablation mouse models, CD301b-expressing macrophages selectively activated proliferation of APs, but not other myofibroblasts. Myofibroblast composition and gene expression changed during aging. Thus, macrophage-fibroblast interactions are important during tissue repair and aging, which may have therapeutic implications for chronic wounds and fibrotic disease. Science , this issue p. eaar2971 ; see also p. 891
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Genetic and pharmacological inactivation of PU.1 enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs.
“Furthermore, genetic and pharmacological inactivation of PU.1 enabled reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs37.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [37]
The transcription factor PU.1 plays a major role in fibroblast polarization and fibrogenesis.
“the transcription factor PU.1, whose expression is silenced in fibroblasts during tissue homeostasis but upregulated in fibrotic disease, has been shown to play a major role in fibroblast polarization and fibrogenesis37.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [37]
PU.1 both polarizes resting fibroblasts and repolarizes ECM-degrading inflammatory fibroblasts to an ECM-producing fibrotic phenotype.
“PU.1 both polarized resting fibroblasts and repolarized ECM-degrading inflammatory fibroblasts to an ECM-producing fibrotic phenotype.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [37]
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- Authors
- Shook, B. A., Wasko, R. R., Rivera-Gonzalez, G. C., Salazar-Gatzimas, E., López-Giráldez, F., Dash, B. C., Muñoz-Rojas, A. R., Aultman, K. D., Zwick, R. K., Lei, V., Arbiser, J. L., Miller-Jensen, K., Clark, D. A., Hsia, H. C., & Horsley, V.
- Affiliations
- Yale University (US)
- Yale Center for Genome Analysis, Yale School of Medicine, New Haven, CT 06510, USA.
- Emory University (US)
- Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
- Corresponding author
- Shook, Brett A.
- Horsley, Valerie
- ORCID
- Venue
- Science
- Published
- 2018-11-23
- Volume
- 362
- Issue
- 6417
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6684198
- OpenAlex
- W2900976549
- Cited by
- 519
- References
- 79
- Citations by year
- 2026: 55 · 2025: 71 · 2024: 77 · 2023: 68 · 2022: 84 · 2021: 73 · 2020: 53 · 2019: 37 · 2018: 1
- FWCI
- 35.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Aging (P30AG21342)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR060295, AR069550)
- New York Stem Cell Foundation (NYSCF-D-F#48)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- myofibroblasts, macrophages, skin wound healing, fibrosis, aging, adipocyte precursors, insulin-like growth factor I, PDGF-C, extracellular matrix deposition, cell proliferation
- MeSH terms
- Animals, Extracellular Matrix, Fibrosis, Keloid, Lymphokines, Macrophages, Mice, Inbred C57BL, Platelet-Derived Growth Factor, Skin, Wound Healing, Skin Aging, Adipocytes, Integrin beta1, Lectins, C-Type, Cell Proliferation, Mice, Myofibroblasts, Transcriptome, Mesenchymal Stem Cells, Re-Epithelialization
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