Dermal Fibroblast CCN1 Expression in Mice Recapitulates Human Skin Dermal Aging
Open accessAbstract
The aging process deleteriously alters the structure and function of dermal collagen. These alterations result in thinning, fragility, wrinkles, laxity, impaired wound healing, and a microenvironment conducive to cancer. However, the key factors responsible for these changes have not been fully elucidated, and relevant models for the study of skin aging progression are lacking. CCN1, a secreted extracellular matrix‒associated matricellular protein, is elevated in dermal fibroblasts in aged human skin. Toward constructing a mouse model to study the key factors involved in skin-aging progression, we demonstrate that transgenic mice, with selective expression of CCN1 in dermal fibroblasts (COL1A2-CCN1), display accelerated skin dermal aging. The aged phenotype in COL1A2-CCN1 mice resembles aged human dermis: the skin is wrinkled and the dermis is thin and composed of loose, disorganized, and fragmented collagen fibrils. These dermal alterations reflect reduced production of collagen due to impaired TGFβ signaling and increased expression of matrix metalloproteinases driving the induction of c-Jun/activator protein-1. Importantly, similar mechanisms drive human dermal aging. Taken together, the data demonstrate that elevated expression of CCN1 by dermal fibroblasts functions as a key mediator of dermal aging. The COL1A2-CCN1 mouse model provides a novel tool for understanding and studying the mechanisms of skin aging and age-related skin disorders.
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Mouse models of UV radiation show increased expression of Mmp1, Mmp2 and Mmp3 and other SASP factors such as TNF, IL-1β and IL-6.
“Mouse models of UV radiation show increased expression of Mmp1, Mmp2 and Mmp3, and of other SASP factors such as TNF, IL-1β and IL-6 (refs. 220–223).”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [222]
The Results and Discussion section on elevated MMP expression (page unavailable) reports increased MMPs in COL1A2-CCN1 mouse fibroblasts. But the mice were a genetic model of dermal aging, not a UV-radiation model, and the elevated enzymes reported were MMP-9, -10, -13, -24 and -27—not MMP-1, -2 or -3. The passages do not report increased TNF, IL-1β or IL-6 in these mice. (LLM, conf=0.86)
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- Authors
- Quan, T., Xiang, Y., Liu, Y., Qin, Z., Yang, Y., Bou-Gharios, G., Voorhees, J. J., Dlugosz, A. A., & Fisher, G. J.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Quan, Taihao
- ORCID
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 141
- Issue
- 4
- Pages
- 1007-1016
- ISSN
- 0022-202X (ISSN-L)
- PMC
- PMC7881053
- OpenAlex
- W3048457623
- Cited by
- 30
- References
- 44
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 3 · 2023: 7 · 2022: 2 · 2021: 1
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- CYR61, skin aging, dermal fibroblasts, TGF-beta signaling, matrix metalloproteinases, transgenic mouse model, extracellular matrix, matricellular proteins
- MeSH terms
- Animals, Cells, Cultured, Collagen, Fibroblasts, Humans, Mice, Transgenic, Promoter Regions, Genetic, Skin Aging, Up-Regulation, Dermis, Models, Animal, Collagen Type I, Mice, Cysteine-Rich Protein 61, HEK293 Cells, Primary Cell Culture
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