ArticleAging cell2016
Reduction of fibroblast size/mechanical force down-regulates TGF-β type II receptor: implications for human skin aging.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 112 citations in OpenAlex.
- Dermal Templates Support Epidermal Regeneration and Maturation Regardless of Cell Donor Age.Tissue engineering. Part A · 2026Article
- Microbiome-Derived Metabolic Signaling in the Gut-Skin Axis: Implications for Nutricosmetics and Healthy Skin Aging.Nutrients · 2026Review
- Leukocyte-Rich Platelet-Rich Plasma (L-PRP) Promotes Rejuvenation of Senescent Fibroblasts and Dermal Remodeling via CCL1-CCR8 Signaling and PKM2 Modulation.International journal of molecular sciences · 2026Article
- From ECM Aging to Mechanobiological Restoration: Injectable Fillers and Dermal Fibroblast Mechanotransduction-A Narrative Review.Gels (Basel, Switzerland) · 2026Review
- Skin Organoids in Proteostasis Research: Early Insights into Aging.Biomolecules & therapeutics · 2026Review
- In vitro modelling of extracellular matrix changes during skin aging: from static 2D to 3D dynamic microphysiological systems.Microsystems & nanoengineering · 2026Review
- Azelaic acid alleviates UVB-induced photoaging in keratinocytes by restoring Smad-dependent TGF-β signaling.Frontiers in medicine · 2026Article
- Integrative Aesthetics: Shaping the Emerging Frontier of Modern Aesthetic Medicine.Clinical, cosmetic and investigational dermatology · 2026Review
- Cell biomechanics on muscle atrophy: from intricate mechanisms to therapeutic frontiers.Annals of medicine · 2025Review
- The Human-Like Collagen Alpha-1 Type V Peptides Strengthen the Dermal Fiber Network and Improve the Regeneration Ability of Cells.Journal of cosmetic dermatology · 2025Article
- ECM Remodeling in Direct Inguinal Hernia: The Role of Aging, Oxidative Stress, and Antioxidants Defenses.Clinics and practice · 2025Review
- 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
- Red light promotes dermis-epidermis remodeling via TGFβ and AKT-mediated collagen dynamics in naturally aging mice.Zoological research · 2025Article
- Collagen supplementation and regenerative health: advances in biomarker detection and smart material integration.Frontiers in nutrition · 2025Review
- Extracellular matrix dysregulation in aging, calcification, and cancer diseases: insights into cellular senescence, inflammation, and novel therapeutic strategies.International journal of biological sciences · 2025Review
- Recent advances in dermal fibroblast senescence and skin aging: unraveling mechanisms and pioneering therapeutic strategies.Frontiers in pharmacology · 2025Review
- LncRNA CRNDE regulates the differentiation of tendon-derived stem cells and enhances rotator cuff injury repair by modulating the miR-337/TGFBR2 axis.International journal of clinical and experimental pathology · 2025Article
- Polynucleotides in Aesthetic Medicine: A Review of Current Practices and Perceived Effectiveness.International journal of molecular sciences · 2024Review
- Emerging Perspectives of YAP/TAZ in Human Skin Epidermal and Dermal Aging.Annals of dermatology · 2024Review
- High-resolution 3-D scanning electron microscopy (SEM) images of DOTSkin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The structural integrity of human skin is largely dependent on the quality of the dermal extracellular matrix (ECM), which is produced, organized, and maintained by dermal fibroblasts. Normally, fibroblasts attach to the ECM and thereby achieve stretched, elongated morphology. A prominent characteristic of dermal fibroblasts in aged skin is reduced size, with decreased elongation and a more rounded, collapsed morphology. Here, we show that reduced size of fibroblasts in mechanically unrestrained three-dimensional collagen lattices coincides with reduced mechanical force, measured by atomic force microscopy. Reduced size/mechanical force specifically down-regulates TGF-β type II receptor (TβRII) and thus impairs TGF-β/Smad signaling pathway. Both TβRII mRNA and protein were decreased, resulting in 90% loss of TGF-β binding to fibroblasts. Down-regulation of TβRII was associated with significantly decreased phosphorylation, DNA-binding, and transcriptional activity of its key downstream effector Smad3 and reduced expression of Smad3-regulated essential ECM components type I collagen, fibronectin, and connective tissue growth factor (CTGF/CCN2). Restoration of TβRII significantly increased TGF-β induction of Smad3 phosphorylation and stimulated expression of ECM components. Reduced expression of TβRII and ECM components in response to reduced fibroblast size/mechanical force was fully reversed by restoring size/mechanical force. Reduced fibroblast size was associated with reduced expression of TβRII and diminished ECM production, in aged human skin. Taken together, these data reveal a novel mechanism that provides a molecular basis for loss of dermal ECM, with concomitant increased fragility, which is a prominent feature of human skin aging.
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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 OpenQuestion graph.