文献类型：期刊文献

英文题名：Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

作者：Zhao, Chenyu[1,3];Yu, Yunyuan[1,2];Yin, Guangrong[1];Xu, Chao[4];Wang, Jiahao[5];Wang, Liangliang[1];Zhao, Gongyin[1,6];Ni, Su[7];Zhang, Haoxing[8];Zhou, Baojun[9];Wang, Yuji[1,6,9]

第一作者：Zhao, Chenyu

通信作者：Wang, YJ[1];Wang, YJ[2];Wang, YJ[3]

机构：[1]Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Changzhou Med Ctr, Dept Orthoped, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[2]Nanjing Med Univ, Longmian Ave 101, Nanjing 211166, Jiangsu, Peoples R China;[3]Dalian Med Univ, Sch Grad, 9 West Sect,Shunnan Rd, Dalian 116044, Peoples R China;[4]Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Truma Cent, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[5]Chengdu Sport Univ, Affiliated Sport Hosp CDSU, Dept Orthoped, 251 Wuhouci St, Chengdu 610041, Peoples R China;[6]Mayo Clin, Dept Orthoped Surg & Biochem & Mol Biol, Rochester, MN 55905 USA;[7]Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Med Res Ctr, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[8]Shenzhen Univ, Coll Life Sci & Oceanog, Guangdong Prov Key Lab Genome Stabil & Dis Prevent, Shenzhen 518055, Peoples R China;[9]Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China

第一机构：Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Changzhou Med Ctr, Dept Orthoped, 29 Xinglong Alley, Changzhou 213003, Peoples R China

通信机构：[1]corresponding author), Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Changzhou Med Ctr, Dept Orthoped, 29 Xinglong Alley, Changzhou 213003, Peoples R China;[2]corresponding author), Mayo Clin, Dept Orthoped Surg & Biochem & Mol Biol, Rochester, MN 55905 USA;[3]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, 222 Silong Rd, Baiyin 730900, Peoples R China.|[10735]甘肃中医药大学;

年份：2024

卷号：32

期号：2

起止页码：1277

外文期刊名：INFLAMMOPHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-85185918171);WOS:【SCI-EXPANDED(收录号:WOS:001170939400001)】；

基金：This study was supported by the National Natural Science Foundation of China (82002321) to Liangliang Wang, the Clinical Research Project of Changzhou Medical Center of Nanjing Medical University (CMCB202208) and the Major Research Project of Changzhou Commission of Health (ZD202217). We want to thank all the patients who participated in our study.

语种：英文

外文关键词：Ferroptosis; Rheumatoid arthritis; Sulfasalazine; Fibroblast-like synoviocyte

摘要：ObjectiveFerroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA.MethodsCCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund's adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining.ResultsThe results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53.ConclusionsSulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.