1. MiR-204/-211 double knockout exacerbates rheumatoid arthritis progression by promoting splenic inflammation.
- Author
-
Wang QS, Fan KJ, Teng H, Liu J, Yang YL, Chen D, and Wang TY
- Subjects
- Animals, Male, Mice, Disease Progression, Inflammation, Interleukin-1beta metabolism, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Tumor Necrosis Factor-alpha metabolism, Arthritis, Experimental immunology, Arthritis, Experimental pathology, Arthritis, Experimental genetics, Arthritis, Rheumatoid genetics, Arthritis, Rheumatoid immunology, MicroRNAs genetics, Spleen pathology, Spleen immunology
- Abstract
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-1β (IL-1β), tumor necrosis factor-α (TNF-α), 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-1β, TNF-α, and SSRP1 expression. AAV-shSSRP1 injection in CIA dKO mice significantly reduced spleen inflammation scores, IL-1β and TNF-α 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF