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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2020

01-12-2020 | Rheumatoid Arthritis | Research article

Intervening upregulated SLC7A5 could mitigate inflammatory mediator by mTOR-P70S6K signal in rheumatoid arthritis synoviocytes

Authors: Jing Xu, Congshan Jiang, Yongsong Cai, Yuanxu Guo, Xipeng Wang, Jiaxiang Zhang, Jiawen Xu, Ke Xu, Wenhua Zhu, Si Wang, Fujun Zhang, Manman Geng, Yan Han, Qilan Ning, Peng Xu, Liesu Meng, Shemin Lu

Published in: Arthritis Research & Therapy | Issue 1/2020

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Abstract

Objective

The disruption of metabolic events and changes to nutrient and oxygen availability due to sustained inflammation in RA increases the demand of bioenergetic and biosynthetic processes within the damaged tissue. The current study aimed to understand the molecular mechanisms of SLC7A5 (amino acid transporter) in synoviocytes of RA patients.

Methods

Synovial tissues were obtained from OA and RA patients. Fibroblast-like synoviocytes (FLS) were isolated, and SLC7A5 expression was examined by using RT-qPCR, immunofluorescence, and Western blotting. RNAi and antibody blocking treatments were used to knockdown SLC7A5 expression or to block its transporter activities. mTOR activity assay and MMP expression levels were monitored in RA FLS under amino acid deprivation or nutrient-rich conditions.

Results

RA FLS displayed significantly upregulated expression of SLC7A5 compared to OA FLS. Cytokine IL-1β was found to play a crucial role in upregulating SLC7A5 expression via the NF-κB pathway. Intervening SLC7A5 expression with RNAi or blocking its function by monoclonal antibody ameliorated MMP3 and MMP13 protein expression. Conversely, upregulation of SLC7A5 or tryptophan supplementation enhanced mTOR-P70S6K signals which promoted the protein translation of MMP3 and MMP13 in RA FLS.

Conclusion

Activated NF-κB pathway upregulates SLC7A5, which enhances the mTOR-P70S6K activity and MMP3 and MMP13 expression in RA FLS.
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Metadata
Title
Intervening upregulated SLC7A5 could mitigate inflammatory mediator by mTOR-P70S6K signal in rheumatoid arthritis synoviocytes
Authors
Jing Xu
Congshan Jiang
Yongsong Cai
Yuanxu Guo
Xipeng Wang
Jiaxiang Zhang
Jiawen Xu
Ke Xu
Wenhua Zhu
Si Wang
Fujun Zhang
Manman Geng
Yan Han
Qilan Ning
Peng Xu
Liesu Meng
Shemin Lu
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2020
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-020-02296-8

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