| First Author | Wang QS | Year | 2024 |
| Journal | Int Immunopharmacol | Volume | 140 |
| Pages | 112850 | PubMed ID | 39116488 |
| Mgi Jnum | J:354022 | Mgi Id | MGI:7717138 |
| Doi | 10.1016/j.intimp.2024.112850 | Citation | Wang QS, et al. (2024) MiR-204/-211 double knockout exacerbates rheumatoid arthritis progression by promoting splenic inflammation. Int Immunopharmacol 140:112850 |
| abstractText | OBJECTIVE: Collagen-induced arthritis (CIA) model was induced in C57BL/6 wild-type (wt) and C57BL/6 miR-204/-211 double-knockout (dKO) mice to investigate the role of miR-204/-211 in suppressing splenic inflammation in rheumatoid arthritis (RA). METHODS: Differences of miR-204/-211 and structure-specific recognition protein 1 (SSRP1) in the spleen of DBA/1J wt and CIA mice were detected via PCR and immunohistochemistry. CIA was induced in both C57BL/6 wt and C57BL/6 miR-204/-211 dKO mice, and the onset of CIA and disease severity were statistically analyzed. Immunohistochemistry staining of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and SSRP1 in spleen or knee joints was performed and analyzed. In CIA miR-204/-211 dKO mice, AAV-shSSRP1 was intra-articularly injected, with both the AAV-shRNA Ctrl and AAV-shRNA Ctrl CIA groups receiving the same dose of AAV-shRNA. Spleen sections were stained with hematoxylin and eosin (H&E). RESULTS: Compared to wt mouse spleens, aberrant expression of miR-204/-211 and SSRP1 was observed in the spleens of CIA mice. Immunized dKO mice exhibited a higher incidence of CIA onset and a more exacerbated RA disease phenotype, characterized by increased spleen inflammation score and elevated levels of IL-1beta, TNF-alpha, and SSRP1 expression. AAV-shSSRP1 injection in CIA dKO mice significantly reduced spleen inflammation scores, IL-1beta and TNF-alpha expression levels, and down-regulated Ki-67 expression compared to CIA dKO mice. CONCLUSION: Knockout of miR-204/-211 exacerbated the onset of CIA in C57BL/6 mice, while miR-204/-211 played a protective role against the progression of splenic inflammatory and proliferative progression in RA by targeting SSRP1. |
