دورية أكاديمية
Protein tyrosine phosphatase 1B as a therapeutic target for Graves' orbitopathy in an in vitro model
| العنوان: | Protein tyrosine phosphatase 1B as a therapeutic target for Graves' orbitopathy in an in vitro model |
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| المساهمون: | Hyeong Ju Byeon, Ji-Young Kim, JaeSang Ko, Eun Jig Lee, Kikkawa Don, Jin Sook Yoon, Ko, Jaesang |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Animals, Apoptosis, Cattle, Cell Survival, Cytokines / biosynthesis, Endoplasmic Reticulum Stress, Female, Fibroblasts / drug effects, Fibroblasts / metabolism, Fibroblasts / pathology, Gene Silencing, Graves Ophthalmopathy / enzymology, Graves Ophthalmopathy / pathology, Graves Ophthalmopathy / therapy, Humans, In Vitro Techniques, Inflammation Mediators / metabolism, Male, Middle Aged, Oxidative Stress, Prefrontal Cortex / drug effects, Prefrontal Cortex / metabolism, Prefrontal Cortex / pathology, Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors, Non-Receptor Type 1 / genetics, Non-Receptor Type 1 / metabolism, RNA, Small Interfering / genetics |
| الوصف: | Graves' orbitopathy (GO) is characterised in early stages by orbital fibroblast inflammation, which can be aggravated by oxidative stress and often leads to fibrosis. Protein tyrosine protein 1B (PTP1B) is a regulator of inflammation and a therapeutic target in diabetes. We investigated the role of PTP1B in the GO mechanism using orbital fibroblasts from GO and healthy non-GO subjects. After 24 hours of transfection with PTPN1 siRNA, the fibroblasts were exposed to interleukin (IL)-1β, cigarette smoke extract (CSE), H2O2, and transforming growth factor (TGF)-β stimulations. Inflammatory cytokines and fibrosis-related proteins were analysed using western blotting and/or enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) release was detected using an oxidant-sensitive fluorescent probe. IL-1β, tumor necrosis factor (TNF)-α, bovine thyroid stimulating hormone (bTSH), high-affinity human stimulatory monoclonal antibody of TSH receptor (M22), and insulin-like growth factor-1 (IGF-1) significantly increased PTP1B protein production in GO and non-GO fibroblasts. PTPN1 silencing significantly blocked IL-1β-induced inflammatory cytokine production, CSE- and H2O2-induced ROS synthesis, and TGF-β-induced expression of collagen Iα, α-smooth muscle actin (SMA), and fibronectin in GO fibroblasts. Silencing PTPN1 also decreased phosphorylation levels of Akt, p38, and c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER)-stress response proteins in GO cells. PTP1B may be a potential therapeutic target of anti-inflammatory, anti-oxidant and anti-fibrotic treatment of GO. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | PLOS ONE; J02540; OAK-2020-08277; https://ir.ymlib.yonsei.ac.kr/handle/22282913/181569Test; T202006070; PLOS ONE, Vol.15(8) : e0237015, 2020-08 |
| DOI: | 10.1371/journal.pone.0237015 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0237015Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/181569Test |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.5914DC45 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0237015 |