Interferon-α2b-Induced RARRES3 Upregulation Inhibits Hypertrophic Scar Fibroblasts' Proliferation and Migration Through Wnt/β-Catenin Pathway Suppression
- 1 January 2023
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Interferon & Cytokine Research
- Vol. 43 (1), 23-34
- https://doi.org/10.1089/jir.2022.0183
Abstract
Hypertrophic scar (HS) is a severe skin fibrotic disorder with unclear pathogenesis. Interferon-α2b (IFN-α2b) exerts inhibitory effects on HS in vivo and in vitro; however, the exact mechanism remains unclear. In this study, we aimed to evaluate the inhibitory effects of IFN-α2b on hypertrophic scar fibroblasts' (HSFs) proliferation and migration, and to further investigate the associated molecular mechanism. Cell Counting Kit-8 and CyQUANT assays were used to assess HSFs' proliferation; wound healing and Transwell assays were used to assess HSFs' migration; real-time quantitative polymerase chain reaction and Western blotting were used to detect messenger RNA and protein levels, respectively, of related genes; bioinformatics analysis was performed to predict the downstream target of IFN-α2b. Our findings are as follows: (1) IFN-α2b inhibited HSFs' proliferation and migration in a dose-dependent manner. (2) IFN-α2b inhibited HSFs' proliferation and migration by suppressing the Wnt/β-catenin pathway. (3) Retinoic-acid receptor responder 3 (RARRES3) was predicted as a functional downstream molecule of IFN-α2b, which was low in HSFs. (4) IFN-α2b inhibited HSF phenotypes and the Wnt/β-catenin pathway by upregulating RARRES3 expression. (5) RARRES3 restrained HSFs' proliferation and migration by repressing the Wnt/β-catenin pathway. In conclusion, IFN-α2b-induced RARRES3 upregulation inhibited HSFs' proliferation and migration through Wnt/β-catenin pathway suppression.Keywords
This publication has 23 references indexed in Scilit:
- TIG3: An Important Regulator of Keratinocyte Proliferation and SurvivalJournal of Investigative Dermatology, 2014
- The Antiviral Cytokines IFN-α and IFN-β Modulate Parietal Epithelial Cells and Promote Podocyte LossThe American Journal of Pathology, 2013
- STAT2 deficiency and susceptibility to viral illness in humansProceedings of the National Academy of Sciences of the United States of America, 2013
- Interferon-α2b and transforming growth factor-β1 treatments on HCC cell lines: Are Wnt/β-catenin pathway and Smads signaling connected in hepatocellular carcinoma?Biochemical Pharmacology, 2011
- TIG3 Tumor Suppressor-Dependent Organelle Redistribution and Apoptosis in Skin Cancer CellsPLOS ONE, 2011
- NCBI GEO: archive for high-throughput functional genomic dataNucleic Acids Research, 2009
- Upregulation of the Wnt/?-catenin Pathway Induced by Transforming Growth Factor-? in Hypertrophic Scars and KeloidsActa Dermato-Venereologica, 2006
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Transforming Growth Factor-betamRNA and Protein in Hypertrophic Scar Tissues and Fibroblasts: Antagonism by IFN-alphaand IFN-gammaIn VitroandIn VivoJournal of Interferon & Cytokine Research, 2000
- Transforming Growth Factor-β in Thermally Injured Patients with Hypertrophic Scars: Effects of Interferon α-2bPlastic and Reconstructive Surgery, 1998