ArticleMedical science monitor : international medical journal of experimental and clinical research2020
The Effects of the Transforming Growth Factor-β1 (TGF-β1) Signaling Pathway on Cell Proliferation and Cell Migration are Mediated by Ubiquitin Specific Protease 4 (USP4) in Hypertrophic Scar Tissue and Primary Fibroblast Cultures.
Article in Medical science monitor : international medical journal of experimental and clinical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Network Meta-Analysis of Different Clinical Commonly Used Drugs for the Treatment of Hypertrophic Scar and Keloid.Frontiers in medicine · 2021Pooled it
- Deubiquitinases as Regulators and Therapeutic Targets in Vascular Diseases.International journal of molecular sciences · 2026Review
- Current therapeutic strategies and available research models for investigating hypertrophic scars.Frontiers in pharmacology · 2026Review
- Innovative research on predicting skin flaps necrosis through quantification of the USP4/TNFAIP2 regulated 'M1 macrophages-Tregs axis' via skin barrier monitoring technology.Burns & trauma · 2026Article
- Melatonin-engineered MSCs-exosomes deliver USP4 to stabilise ARNTL and inhibit clock rhythmic ferroptosis for enhanced flap survival.Clinical and translational medicine · 2026Article
- Role of Cytokines in Wound Healing Following Wound Catheter Analgesia in Rats.Veterinary sciences · 2025Article
- Integrated plasma metabolomic and proteomic analysis uncover the effects and mechanisms of isotretinoin in severe acne.Frontiers in pharmacology · 2025Article
- SIRT1 Activation Suppresses Corneal Endothelial-Mesenchymal Transition via the TGF-β/Smad2/3 Pathway.Current issues in molecular biology · 2024Article
- Macrophage Polarization: A Novel Target and Strategy for Pathological Scarring.Tissue engineering and regenerative medicine · 2024Review
- USP4 promotes PTC progression by stabilizing LDHA and activating the MAPK and AKT signaling pathway.Aging · 2024Article
- Metformin attenuates multiple myeloma cell proliferation and encourages apoptosis by suppressing METTL3-mediated m6A methylation of THRAP3, RBM25, and USP4.Cell cycle (Georgetown, Tex.) · 2023Article
- Binding of Vialinin A andMolecules (Basel, Switzerland) · 2022Article
- Effect of Mortalin on Scar Formation in Human Dermal Fibroblasts and a Rat Incisional Scar Model.International journal of molecular sciences · 2022Article
- Circular RNA HECTD1 knockdown inhibits transforming growth factor-beta/ small mothers against decapentaplegic (TGF-β/Smad) signaling to reduce hypertrophic scar fibrosis.Bioengineered · 2022Article
- LncRNA PICSAR binds to miR-485-5p and activates TGF-β1/Smad to promote abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and excessive deposition of extracellular matrix (ECM).Medical molecular morphology · 2021Article
- [Expression of microRNA-296 in rabbit hypertrophic scars and its role to human fibroblasts].Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns · 2021Article
- Anlotinib Inhibits PFKFB3-Driven Glycolysis in Myofibroblasts to Reverse Pulmonary Fibrosis.Frontiers in pharmacology · 2021Article
- Spotlight on USP4: Structure, Function, and Regulation.Frontiers in cell and developmental biology · 2021Review
- The Ubiquitin Proteasome System and Skin Fibrosis.Molecular diagnosis & therapy · 2021Review
- Effect of THBS1 on the Biological Function of Hypertrophic Scar Fibroblasts.BioMed research international · 2020Article
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
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND Hypertrophic scar results from an abnormal repair response to trauma in the skin and involves fibroblasts proliferation with increased collagen deposition. Transforming growth factor-ß1 (TGF-ß1) and TGF-ß receptor type I (TGF-ßR1) are involved in tissue repair and are increased by ubiquitin-specific protease 4 (USP4). This study aimed to investigate the effects of TGF-ßR1 and USP4 in human tissue samples of hypertrophic scar and on cell proliferation and cell migration in primary fibroblast cultures in vitro. MATERIAL AND METHODS Skin excision tissue samples with adjacent normal skin were obtained from 15 patients with hypertrophic scar, which provided tissue sections and primary fibroblast culture for analysis. Immunohistochemistry detected the expression of USP4 and TGF-ßR1 in tissue sections. MicroRNA (miRNAs) expression levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to measure protein expression levels. Cultured skin fibroblasts were investigated using immunofluorescence staining. Fibroblast proliferation, apoptosis, and migration were measured with the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and a wound-healing assay, respectively. RESULTS The expression of USP4 and TGF-ßR1 in hypertrophic scar were increased compared with normal skin. Fibroblasts cultured from hypertrophic scar tissue showed increased expression of of USP4 and TGF-ßR1. Fibroblast transfection with USP4 short-interfering RNA (siRNA) resulted in reduced fibroblast proliferation and migration, and increased apoptosis. Downregulation of USP4 inhibited the expression of TGF-ßR1 protein and increased the expression levels of Smad7 protein. CONCLUSIONS USP4 regulated the proliferation, migration, and apoptosis of hypertrophic scar fibroblasts by regulating the TGF-ß1 signaling pathway.
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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.