Academic Journal
Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation
| العنوان: | Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation |
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| المساهمون: | Min Ji Cho, Dong Gwang Lee, Jeong Woong Lee, Byungtae Hwang, Sung-Jin Yoon, Seon-Jin Lee, Young-Jun Park, Seung-Ho Park, Hee Gu Lee, Yong-Hoon Kim, Chul-Ho Lee, Jangwook Lee, Nam-Kyung Lee, Tae-Su Han, Hyun-Soo Cho, Jeong Hee Moon, Ga Seul Lee, Kwang-Hee Bae, Geum-Sook Hwang, Sang-Hak Lee, Sang J Chung, Sungbo Shim, Jaehyung Cho, Goo Taeg Oh, Young-Guen Kwon, Jong-Gil Park, Jeong-Ki Min, Lee, Snag Hak |
| بيانات النشر: | Oxford Journals |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Animals, Cell Cycle Proteins / metabolism, Endothelial Cells* / metabolism, Humans, Inflammation / genetics, Inflammation / metabolism, Membrane Proteins / metabolism, Mice, NF-kappa B* / metabolism, Protein Tyrosine Phosphatases / metabolism, Signal Transduction, Upstream Stimulatory Factors / metabolism, Atherosclerosis, Cell adhesion molecules, Endothelial cells, Protein phosphatase, Vascular inflammation |
| الوصف: | AIMS: The nuclear factor-κB (NF-κB) signalling pathway plays a critical role in the pathogenesis of multiple vascular diseases. However, in endothelial cells (ECs), the molecular mechanisms responsible for the negative regulation of the NF-κB pathway are poorly understood. In this study, we investigated a novel role for protein tyrosine phosphatase type IVA1 (PTP4A1) in NF-κB signalling in ECs. METHODS AND RESULTS: In human tissues, human umbilical artery ECs, and mouse models for loss of function and gain of function of PTP4A1, we conducted histological analysis, immunostaining, laser-captured microdissection assay, lentiviral infection, small interfering RNA transfection, quantitative real-time PCR and reverse transcription-PCR, as well as luciferase reporter gene and chromatin immunoprecipitation assays. Short hairpin RNA-mediated knockdown of PTP4A1 and overexpression of PTP4A1 in ECs indicated that PTP4A1 is critical for inhibiting the expression of cell adhesion molecules (CAMs). PTP4A1 increased the transcriptional activity of upstream stimulatory factor 1 (USF1) by dephosphorylating its S309 residue and subsequently inducing the transcription of tumour necrosis factor-alpha-induced protein 3 (TNFAIP3/A20) and the inhibition of NF-κB activity. Studies on Ptp4a1 knockout or transgenic mice demonstrated that PTP4A1 potently regulates the interleukin 1β-induced expression of CAMs in vivo. In addition, we verified that PTP4A1 deficiency in apolipoprotein E knockout mice exacerbated high-fat high-cholesterol diet-induced atherogenesis with upregulated expression of CAMs. CONCLUSION: Our data indicate that PTP4A1 is a novel negative regulator of vascular inflammation by inducing USF1/A20 axis-mediated NF-κB inactivation. Therefore, the expression and/or activation of PTP4A1 in ECs might be useful for the treatment of vascular inflammatory diseases. © The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0008-6363 1755-3245 |
| Relation: | CARDIOVASCULAR RESEARCH; J00464; OAK-2023-02060; https://ir.ymlib.yonsei.ac.kr/handle/22282913/195554; https://academic.oup.com/cardiovascres/article/119/5/1265/6936587; T202303617; CARDIOVASCULAR RESEARCH, Vol.119(5) : 1265-1278, 2023-05 |
| DOI: | 10.1093/cvr/cvac193 |
| الاتاحة: | https://ir.ymlib.yonsei.ac.kr/handle/22282913/195554 https://doi.org/10.1093/cvr/cvac193 https://academic.oup.com/cardiovascres/article/119/5/1265/6936587 |
| Rights: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.BE8A4DDC |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00086363 17553245 |
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| DOI: | 10.1093/cvr/cvac193 |