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ROS-Dependent Lipid Peroxidation and Reliant Antioxidant Ferroptosis-Suppressor-Protein 1 in Rheumatoid Arthritis: a Covert Clue for Potential Therapy

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Abstract

Rheumatoid arthritis (RA) is a common systemic autoimmune disease with a prevalence of about 1% in which genetic and environmental risk factors both participate in performance of disease. Though several studies contributed in identifying its etiology and pathogenesis, the underlying mechanisms are still unknown. To date, so as palliative for RA, cure strategies are still popular. Hypoxia and oxidative stress are implicated to RA development and subsequent ROS-mediated cell death which is a critical feature for RA progression. As for cell death and lipid peroxidation, ferroptosis is a newly discovered, iron-dependent, and non-apoptotic cell death which draws various attention due to its potential strategies for cancer therapy. Meanwhile, ferroptosis-suppressor-protein 1 (FSP1) is recently identified as a seminal breakthrough owing to its property of versus ferroptosis. By virtue of the complicated research progress on FSP1 with ferroptosis, in this review, we summarize the whole region of relevance between ROS and RA. Taken together, we hypothesize that ROS accompanied with ferroptosis may function as a reciprocal with cell death that interplays with RA; besides, FSP1 might become a potential therapeutic target for RA because of its potential interaction with TNF-α/ROS-positive feedback loop. This review systematically concludes the previous understandings about identification of ROS and FSP1 and, in turn, aims to provide references for further achievements of them and hints on elucidation of its thorough underlying mechanisms.

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Funding

This work was supported by the Natural Science Foundation of Shandong Province (Grant No. BS2015SW028, ZR2016HM53, and ZR2019MH05), Key Research and Development Projects of Shandong Province (Grant No. 2015GSF118115), the Cross-disciplinary Fund of Shandong University (Grant No. 2018JC007), the National Natural Science Foundation of China (Grant No. 81572191, 81501880, and 81602761), and the College Student Science and Technology Innovation Fund of Shandong University (Grant No. 2019369).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Zhaoxiang Xie, Yunpeng Zhao & Cheng Qiu

  2. Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China

    Zhaoxiang Xie, Haodong Hou, Ran An & Cheng Qiu

  3. College of Stomatology, Qingdao University, Qingdao, 266071, Shandong, People’s Republic of China

    Dan Luo

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  1. Zhaoxiang Xie
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  4. Ran An
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  5. Yunpeng Zhao
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  6. Cheng Qiu
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Contributions

CQ, YZ, and ZX performed the literature search and were major contributors in the writing of the manuscript. DL, HH, and RA provided suggestions and edited the paper. All authors read and approved the final manuscript.

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Correspondence to Yunpeng Zhao or Cheng Qiu.

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Xie, Z., Hou, H., Luo, D. et al. ROS-Dependent Lipid Peroxidation and Reliant Antioxidant Ferroptosis-Suppressor-Protein 1 in Rheumatoid Arthritis: a Covert Clue for Potential Therapy. Inflammation 44, 35–47 (2021). https://doi.org/10.1007/s10753-020-01338-2

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