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

• DOI: 10.34133/research.0459
• Publication Date: 2024-08-06T16:50:24Z
• Authors: Qiuyan Guo; Qixin Wang; Jiayun Chen; Minghong Zhao; Tianming Lu; Zuchang Guo; Chen Wang; Yin Kwan Wong; Xueling He; Lin Chen; Wenjing Zhang; Chuanhao Dai; Shengnan Shen; Huanhuan Pang; Fei Xia; Chong Qiu; Daoyuan Xie; Jigang Wang
• Keywords: MMP3; Dihydroartemisinin; MMP2; MMP9

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