1. Wenhua Juanbi Recipe Attenuates Rheumatoid Arthritis via Inhibiting miRNA-146a-Mediated Autophagy
- Author
-
Haili Zhou, Liuyun Huang, Kuijun Zhan, and Xide Liu
- Subjects
General Immunology and Microbiology ,Article Subject ,TOR Serine-Threonine Kinases ,General Medicine ,Arthritis, Experimental ,General Biochemistry, Genetics and Molecular Biology ,Rats ,Arthritis, Rheumatoid ,Phosphatidylinositol 3-Kinases ,MicroRNAs ,Autophagy ,Animals ,Beclin-1 ,Rats, Wistar ,Proto-Oncogene Proteins c-akt ,bcl-2-Associated X Protein - Abstract
Background. Wenhua Juanbi Recipe (WJR) is widely used for the treatment of rheumatoid arthritis (RA) in China. However, its mechanism of action remains unclear. This study was designed to investigate the potential therapeutic effects of WJR on the proliferation and apoptosis of synovial fibroblasts in RA and its efficacy in inhibiting miRNA-146a-mediated cellular autophagy. Methods. A collagen-induced arthritis (CIA) Wistar rat model was established. The model rats were administered WJR or methotrexate (MTX) to assess the therapeutic effect of the drugs. The chemical components of WJR were analyzed using UPLC-Q/TOF-MS. Histological changes; miRNA-146a, ATG5, ATG7, ATG12, Beclin1, LC3II, Bax, and Bcl2 expression; synovial apoptosis; and cellular proliferation were assessed. Primary synovial fibroblasts (FLS) were cultured in vitro using tissue block and transfected with miRNA-146a; an autophagy inducer was added to FLS, inhibiting the PI3K/AKT/mTOR pathway. FLS were cocultured with WJR-containing serum to observe the effects of miRNA-146a-mediated autophagy via the PI3K/AKT/mTOR pathway on CIA-affected rats. Results. Forty and thirty-one compounds were identified in WJR in the positive and negative ion modes, respectively. WJR significantly reduced toe swelling, arthritis scores, and expression of miRNA-146a and autophagy genes (ATG5, ATG7, ATG12, Beclin1, LC32, and Bcl2). Moreover, Bax expression, apoptosis, and attenuated proliferation were observed in rats. WJR could, therefore, regulate autophagy by influencing the miRNA-146a-mediated PI3K/AKT/mTOR pathway, which induces apoptosis and proliferation of FLS. Conclusion. WJR can inhibit autophagy, apoptosis, and proliferation in a CIA rat model by inhibiting the miRNA-146a-mediated PI3K/AKT/mTOR pathway.
- Published
- 2022
- Full Text
- View/download PDF