ArticleBioFactors (Oxford, England)2019
Senescent dermal fibroblasts negatively influence fibroblast extracellular matrix-related gene expression partly via secretion of complement factor D.
Article in BioFactors (Oxford, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- The Zinc-Senescence Axis in Skin Aging and Wound Healing: A Narrative Review.International journal of molecular sciences · 2026Review
- Adipocytes as core drivers of skin aging and novel targets for regeneration.Biogerontology · 2026Review
- Allele-specific RNAi therapy corrects an extracellular matrix defect in Schuurs-Hoeijmakers syndrome.American journal of human genetics · 2025Article
- The states of senescent cells.Biochemical Society transactions · 2025Review
- Transcriptome-wide analysis reveals potential roles of CFD and ANGPTL4 in fibroblasts regulating B cell lineage for extracellular matrix-driven clustering and novel avenues for immunotherapy in breast cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- The complement pathway and the pathophysiology of fibroproliferative cutaneous scarring.Frontiers in immunology · 2025Review
- Biological Aging Exhibits an Inverted J-Shaped Relationship with Stress Urinary Incontinence in Women.International journal of women's health · 2025Article
- Recent advances in dermal fibroblast senescence and skin aging: unraveling mechanisms and pioneering therapeutic strategies.Frontiers in pharmacology · 2025Review
- Rapamycin Attenuates HTissue engineering and regenerative medicine · 2024Article
- Metformin suppresses esophageal cancer progression through the radiation‑induced cellular senescence of cancer‑associated fibroblasts.Oncology reports · 2024Article
- Cellular senescence and SASP in tumor progression and therapeutic opportunities.Molecular cancer · 2024Review
- Human fetal dermal fibroblast-myeloid cell diversity is characterized by dominance of pro-healing Annexin1-FPR1 signaling.iScience · 2023Article
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- Skin aging from mechanisms to interventions: focusing on dermal aging.Frontiers in physiology · 2023Review
- C1QC, VSIG4, and CFD as Potential Peripheral Blood Biomarkers in Atrial Fibrillation-Related Cardioembolic Stroke.Oxidative medicine and cellular longevity · 2023Article
- Low-molecular weight inhibitors of the alternative complement pathway.Immunological reviews · 2023Review
- Bioactive Bacterial Nanocellulose Membranes Enriched withMaterials (Basel, Switzerland) · 2022Article
- Chemical Composition and Effect against Skin Alterations of Bioactive Extracts Obtained by the Hydrodistillation ofPharmaceutics · 2022Article
- Effects of exogenous melatonin on expressional differences of immune-related genes in cashmere goats.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is associated with a decrease of extracellular matrix and an increase of senescent cells in the dermal layer. Here, to examine whether and how senescent cells are involved in aging-related deterioration of the dermal layer, we cocultured dermal young fibroblasts (low-passage number) with senescent cells (high-passage number) in Transwells, in which the two cell types are separated by a semipermeable membrane. Young fibroblasts in coculture showed decreased collagen type I alpha 1 chain and elastin gene expression, and increased matrix metalloproteinase 1 (MMP1) gene expression. To identify causative factors, we compared gene expression of young and senescent cells and selected candidate secretory factors whose expression was increased by ≥2.5 in senescent fibroblasts. Then, we used siRNAs to knock down each of the 11 candidate genes in senescent fibroblasts in the coculture system. Knockdown of complement factor D (CFD) in senescent fibroblasts significantly reduced the increase of MMP1 in the cocultured young fibroblasts. In monocultures, treatment of young fibroblasts with CFD resulted in increased MMP1 gene expression, while knockdown of CFD in senescent fibroblasts decreased MMP1 gene expression. In addition, production of CFD was increased in culture medium of untreated senescent fibroblasts. Furthermore, CFD gene and protein expression were increased in the dermal layer of skin specimens from aged subjects (>70 years old), compared to young subjects (<20 years old). Overall, these results suggest that senescent cells negatively influence matrix production and promote degradation of nearby fibroblasts in the dermal layer, in part through secretion of CFD.
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