ArticleJID innovations : skin science from molecules to population health2022
Age-Related Downregulation of CCN2 Is Regulated by Cell Size in a YAP/TAZ-Dependent Manner in Human Dermal Fibroblasts: Impact on Dermal Aging.
Article in JID innovations : skin science from molecules to population health, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- In vitro modelling of extracellular matrix changes during skin aging: from static 2D to 3D dynamic microphysiological systems.Microsystems & nanoengineering · 2026Review
- Integrin α11β1 as a Key Collagen Receptor in Human Skin Dermis: Insight into Fibroblast Function and Skin Dermal Aging.The Journal of investigative dermatology · 2025Article
- CCN Proteins as Matricellular Regulators of Bone in Aging and Disease.Current osteoporosis reports · 2025Review
- CCN2 functions as a modulator of cell cycle regulation in human dermal fibroblasts.Journal of cell communication and signaling · 2025Article
- Remodeling of cytoskeleton, chromatin, and gene expression during mechanical rejuvenation of aged human dermal fibroblasts.Molecular biology of the cell · 2025Article
- Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.International journal of biological sciences · 2025Review
- Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases.International journal of molecular sciences · 2024Review
- Fibroblast Yap/Taz Signaling in Extracellular Matrix Homeostasis and Tissue Fibrosis.Journal of clinical medicine · 2024Review
- Emerging Perspectives of YAP/TAZ in Human Skin Epidermal and Dermal Aging.Annals of dermatology · 2024Review
- Molecular insights of human skin epidermal and dermal aging.Journal of dermatological science · 2023Review
- Matricellular Proteins in the Homeostasis, Regeneration, and Aging of Skin.International journal of molecular sciences · 2023Review
- CCN proteins: opportunities for clinical studies-a personal perspective.Journal of cell communication and signaling · 2023Review
- Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
CCN2, a member of the CCN family of matricellular proteins, is a key mediator and biomarker of tissue fibrosis. We previously reported that CCN2 is significantly reduced in aged human dermis, which contributes to dermal aging through the downregulation of collagen production, the major structural protein in the skin. In this study, we investigated the underlying mechanisms of the age-related downregulation of CCN2 in human skin dermal fibroblasts. Dermal fibroblasts isolation and laser-capture microdissection‒coupled RT-PCR from human skin confirmed that age-related reduction of CCN2 expression is regulated by epigenetics. Mechanistic investigation revealed that age-related reduction of CCN2 is regulated by impaired dermal fibroblast spreading/cell size, which is a prominent feature of aged dermal fibroblasts in vivo. Gain-of-function and loss-of-function analysis confirmed that age-related downregulation of CCN2 is regulated by YAP/TAZ in response to reduced cell size. We further confirmed that restoration of dermal fibroblast size rapidly reversed the downregulation of CCN2 in a YAP/TAZ-dependent manner. Finally, we confirmed that reduced YAP/TAZ nuclear staining is accompanied by loss of CCN2 in aged human skin in vivo. Our data reveal a mechanism by which age-related reduction in fibroblast spreading/size drives YAP/TAZ-dependent downregulation of CCN2 expression, which in turn contributes to loss of collagen in aged human skin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.