دورية أكاديمية
ASCT2-mediated glutamine uptake promotes Th1 differentiation via ROS-EGR1-PAC1 pathway in oral lichen planus.
| العنوان: | ASCT2-mediated glutamine uptake promotes Th1 differentiation via ROS-EGR1-PAC1 pathway in oral lichen planus. |
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| المؤلفون: | Li W; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Ling Z; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Wang J; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Su Z; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Lu J; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China., Yang X; Department of Periodontology, Stomatological Hospital, Southern Medical University, Guangzhou, China. Electronic address: yangxi53@126.com., Cheng B; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. Electronic address: Chengbin@mail.sysu.edu.cn., Tao X; Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. Electronic address: taoxiaoa@mail.sysu.edu.cn. |
| المصدر: | Biochemical pharmacology [Biochem Pharmacol] 2023 Oct; Vol. 216, pp. 115767. Date of Electronic Publication: 2023 Aug 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| مواضيع طبية MeSH: | Glutamine*/metabolism , Lichen Planus, Oral* , Amino Acid Transport System ASC*/metabolism, Humans ; Alanine ; Cell Differentiation ; Cysteine ; Early Growth Response Protein 1 ; Reactive Oxygen Species/metabolism |
| مستخلص: | Oral lichen planus (OLP) is a T cell-mediated autoimmune disease of oral mucosa concerning with the redox imbalance. Although glutamine uptake mediated by alanine-serine-cysteine transporter 2 (ASCT2) is critical to T cell differentiation, the exact mechanism remains ambiguous. Here, we elucidate a novel regulatory mechanism of ASCT2-mediated uptake in the differentiation and proliferation of T cells through maintaining redox balance in OLP. The results of immunohistochemistry (IHC) showed that both ASCT2 and glutaminase (GLS) were obviously upregulated compared to controls in OLP. Moreover, correlation analyses indicated that ASCT2 expression was significantly related to GLS level. Interestingly, the upregulation of glutamine metabolism in epithelial layer was consistent with that in lamina propria. Functional assays in vitro revealed the positive association between glutamine metabolism and lymphocytes infiltration. Additionally, multiplex immunohistochemistry (mIHC) uncovered a stronger colocalization among ASCT2 and CD4 and IFN-γ, which was further demonstrated by human Th1 differentiation assay in vitro. Mechanistically, targeting glutamine uptake through interference with ASCT2 using L-γ-Glutamyl-p-nitroanilide (GPNA) decreased the glutamine uptake of T cells and leaded to the accumulation of intracellular reactive oxygen species (ROS), which promoted dual specificity phosphatase 2 (DUSP2/PAC1) expression through activation of early growth response 1 (EGR1) to induce dephosphorylation of signal transducer and activator of transcription 3 (STAT3) and inhibit Th1 differentiation in turn. These results demonstrated that glutamine uptake mediated by ASCT2 induced Th1 differentiation by ROS-EGR1-PAC1 pathway, and restoring the redox dynamic balance through targeting ASCT2 may be a potential treatment for T cell-mediated autoimmune diseases. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: ASCT2; Glutamine; Oral Lichen Planus; PAC1; ROS |
| المشرفين على المادة: | OF5P57N2ZX (Alanine) K848JZ4886 (Cysteine) 0 (Early Growth Response Protein 1) 0 (EGR1 protein, human) 0RH81L854J (Glutamine) 0 (Reactive Oxygen Species) 0 (SLC1A5 protein, human) 0 (Amino Acid Transport System ASC) |
| تواريخ الأحداث: | Date Created: 20230827 Date Completed: 20231113 Latest Revision: 20231113 |
| رمز التحديث: | 20231114 |
| DOI: | 10.1016/j.bcp.2023.115767 |
| PMID: | 37634599 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2023.115767 |