20 April 2020 : Clinical Research
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
Yong Huang1AEG, Yuting Wang1AEG, Xueming Wang1BC, Lixin Lin1DF, Peng Wang1CF, Junjun Sun1BE, Lei Jiang1DF*DOI: 10.12659/MSM.920736
Med Sci Monit 2020; 26:e920736
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-β1 (TGF-β1) and TGF-β receptor type I (TGF-βR1) are involved in tissue repair and are increased by ubiquitin-specific protease 4 (USP4). This study aimed to investigate the effects of TGF-βR1 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-βR1 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-βR1 in hypertrophic scar were increased compared with normal skin. Fibroblasts cultured from hypertrophic scar tissue showed increased expression of of USP4 and TGF-βR1. 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-βR1 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-β1 signaling pathway.
Keywords: Cicatrix, Hypertrophic, Protease Inhibitors, Transforming Growth Factor beta, Collagen, Fibroblasts, Immunohistochemistry, primary cell culture, RNA, Messenger, Receptor, Transforming Growth Factor-beta Type I, Skin, Transforming Growth Factor beta1, Ubiquitin-Specific Proteases
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
15 Apr 2024 : Laboratory Research
The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in OsteoarthritisMed Sci Monit In Press; DOI: 10.12659/MSM.943738
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952