دورية أكاديمية
Inhibition of keloid fibroblast proliferation by artesunate is mediated by targeting the IRE1α/XBP1 signaling pathway and decreasing TGF-β1.
| العنوان: | Inhibition of keloid fibroblast proliferation by artesunate is mediated by targeting the IRE1α/XBP1 signaling pathway and decreasing TGF-β1. |
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| المؤلفون: | Han X; Department of Dermatology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. Electronic address: 361333323@qq.com., Jiang S; Department of Dermatology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Hu C; Department of Dermatology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Wang Y; Department of Dermatology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Zhao L; Department of Dermatology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China., Wang W; Department of Dermatology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. |
| المصدر: | Burns : journal of the International Society for Burn Injuries [Burns] 2024 Jun; Vol. 50 (5), pp. 1259-1268. Date of Electronic Publication: 2024 Mar 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8913178 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1409 (Electronic) Linking ISSN: 03054179 NLM ISO Abbreviation: Burns Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: [Guildford, Surrey, UK] : Butterworths, [c1989- |
| مواضيع طبية MeSH: | Artemisinins*/pharmacology , Artemisinins*/therapeutic use , Artesunate*/pharmacology , Artesunate*/therapeutic use , Cell Proliferation*/drug effects , Endoribonucleases*/metabolism , Endoribonucleases*/genetics , Fibroblasts*/drug effects , Fibroblasts*/metabolism , Keloid*/metabolism , Keloid*/drug therapy , Keloid*/pathology , Keloid*/genetics , Protein Serine-Threonine Kinases*/metabolism , Protein Serine-Threonine Kinases*/genetics , Signal Transduction*/drug effects , Transforming Growth Factor beta1*/metabolism , X-Box Binding Protein 1*/metabolism , X-Box Binding Protein 1*/genetics, Adult ; Female ; Humans ; Male ; Cell Cycle/drug effects ; Cell Survival/drug effects ; Cells, Cultured |
| مستخلص: | Background: Keloid is a benign hyperplastic dermatosis with high recurrence rate and complex pathogenesis. There is no universally effective treatment yet. New therapies and elucidation of pathogenesis are urgently required. Aims: To explore the function of IRE1α/XBP1 in keloid fibroblasts and to investigate the potential mechanism of artesunate in inhibiting keloid hyperplasia. Methods: Human keloid fibroblasts (KFs) were cultured, and the expressions of XBP1 and TGF-β1 were detected by immunohistochemistry. The expression of IRE1 was interfered with through cell transfection and the effects of IRE1 interference on cell proliferation and the cell cycle were assessed using MTS, colony formation assays, and flow cytometry. Detection of the expressions of XBP1 and TGF-β1 by qRT-PCR and Western blot. Then artesunate was applied to a subset of the cells, and its effects on cell viability and the expression of related proteins using the same methods. Results: The IRE1α/XBP1 pathway was activated in KFs. Knocking out the gene IRE1α can inhibit the expression of TGF-β1, in addition, the cell viability and cell cycle progression of KFs were also significantly affected. After artesunate treatment, there was a remarkable reduction in cell proliferation. Meanwhile, the cell cycle of KFs treated with artesunate was blocked in G1 phase.After upregulating the expression of IRE1α and treating KFs with artesunate, both cell cycle and proliferation showed inhibitory effects, and related proteins also exhibited suppressed expression. Conclusions: The IRE1α/XBP1 pathway is activated in keloid, and inhibiting the expression of this pathway can affect the cell proliferation activity. In addition, artesunate also has a significant effect on fibroblast proliferation, and the IRE1α/XBP1 pathway may participate in this process. These findings suggest that IRE1α/XBP1 signal pathway may be a potential target for scar treatment, and artesunate could also be a powerful candidate for keloid treatment. Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest. (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Artesunate; IRE1α/XBP1 signaling pathway; Keloid; Keloid fibroblast; TGF-β1 |
| المشرفين على المادة: | 0 (Artemisinins) 60W3249T9M (Artesunate) EC 3.1.- (Endoribonucleases) EC 2.7.11.1 (ERN1 protein, human) EC 2.7.11.1 (Protein Serine-Threonine Kinases) 0 (Transforming Growth Factor beta1) 0 (X-Box Binding Protein 1) 0 (XBP1 protein, human) 0 (TGFB1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240316 Date Completed: 20240523 Latest Revision: 20240715 |
| رمز التحديث: | 20240715 |
| DOI: | 10.1016/j.burns.2024.03.004 |
| PMID: | 38492983 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1879-1409 |
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| DOI: | 10.1016/j.burns.2024.03.004 |