Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis

Guo, Qiuyan1,2; Wang, Qixin1,2; Chen, Jiayun1,2; Zhao, Minghong1,2; Lu, Tianming1,2; Guo, Zuchang1,2; Wang, Chen1,2; Wong, Yin Kwan3; He, Xueling1,2; Chen, Lin1,2; Zhang, Wenjing4; Dai, Chuanhao1,2; Shen, Shengnan1,2; Pang, Huanhuan1,2; Xia, Fei1,2; Qiu, Chong1,2; Xie, Daoyuan5; Wang, Jigang1,2,6,7,8

2024-09-10

10.34133/research.0459

RESEARCH   影响因子和分区

2096-5168

2639-5274

Rheumatoid arthritis (RA) is an autoimmune disease with features of synovial inflammation, cartilage erosion, bone destruction, and pain and is currently lacking a satisfactory treatment strategy. Dihydroartemisinin (DHA), the active metabolite of artemisinin, has exhibited outstanding suppressive effects on RA without obvious side effects. However, the underlying mechanisms remain unclear, which limits its further clinical application. The purpose of this study is to reveal the pharmacodynamic mechanism of DHA against RA by means of a combination of single-cell RNA sequencing (RNA-seq), proteomics, as well as transcriptomics both in vivo and in vitro. In our results, DHA effectively reduced the degree of redness, swelling, and pain in RA rats and dramatically changed the synovial tissue microenvironment under the pathological state. Within this microenvironment, fibroblasts, macrophages, B cells, and endothelial cells were the major affected cell types, primarily through DHA targeting the extracellular matrix (ECM) structural constituent signaling pathway. In addition, we confirmed that DHA regulated the ECM by modulating matrix metalloproteinase 2 (MMP2) and MMP3 in the synovial tissue of RA rats. Moreover, DHA induced apoptosis in MH7A cells, further validating the bioinformatics data. In conclusion, DHA effectively reduced the inflammatory response and improved the immune microenvironment in synovial tissue by inhibiting MMP2 and MMP3. Our findings provide a basis for the application of DHA in the treatment of RA.

SCI

英语

通讯

Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences["CI2023D003","CI2023E005TS02","CI2023E005TS04"] ; National Natural Science Foundation of China["82141001","82274182","82074098"] ; CACMS Innovation Fund["CI2023E002","CI2021A05101"] ; High Level Chinese Medical Hospital Promotion Project[HLCMHPP2023087] ; Young Elite Scientists Sponsorship Program by CACM[2021QNRC2B29] ; Young Elite Scientists Sponsorship Program by BAST[BYESS2024269] ; Fundamental Research Funds for the Central Public Welfare Research Institutes["ZXKT19018","ZZ14-YQ-050","ZZ14-YQ-055","ZXKT19021","ZZ14-YQ-059","ZZ14-YQ-060","ZZ16-ND-10-05","ZZ 16-ND-10-17","ZZ 16-ND-10-19","ZZ 16-ND-10-23","ZZ17-ND-10-05"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:001312220600001

AMER ASSOC ADVANCEMENT SCIENCE

Web of Science

1.China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China
2.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
3.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore, Singapore
4.Chinese Med Assoc, Beijing 100710, Peoples R China
5.Chengdu Univ Tradit Chinese Med, Deyang Peoples Hosp, Lab Translat Med Res, Deyang 618000, Peoples R China
6.Henan Univ, Sch Pharm, State Key Lab Antiviral Drugs, Kaifeng 475004, Peoples R China
7.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Crit Care MeGuangdong Prov Clin Res Ctr Geria, Guangzhou, Guangdong, Peoples R China
8.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China

Guo, Qiuyan,Wang, Qixin,Chen, Jiayun,et al. Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis[J]. RESEARCH,2024,7.

Guo, Qiuyan.,Wang, Qixin.,Chen, Jiayun.,Zhao, Minghong.,Lu, Tianming.,...&Wang, Jigang.(2024).Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis.RESEARCH,7.

Guo, Qiuyan,et al."Dihydroartemisinin Regulated the MMP-Mediated Cellular Microenvironment to Alleviate Rheumatoid Arthritis".RESEARCH 7(2024).