Complete Freund’s Adjuvant induces a fibroblast-like synoviocytes (FLS) metabolic and migratory phenotype in resident fibroblasts of the inoculated footpad at the earliest stage of adjuvant-induced arthritis Journal Article
| Authors: | González-Chávez, S. A.; Chaparro-Barrera, E.; Alvarado-Jáquez, M. F.; Cuevas-Martínez, R.; Ochoa-Albíztegui, R. E.; Pacheco-Tena, C. |
| Article Title: | Complete Freund’s Adjuvant induces a fibroblast-like synoviocytes (FLS) metabolic and migratory phenotype in resident fibroblasts of the inoculated footpad at the earliest stage of adjuvant-induced arthritis |
| Abstract: | The fibroblast-like synoviocytes (FLS) have a crucial role in the pathogenesis of Rheumatoid Arthritis (RA); however, its precise mechanisms remain partially unknown. The involvement of the fibroblast in activating adjuvant-induced arthritis (AA) has not been previously reported. The objective was to describe the participation of footpads’ fibroblasts in the critical initial process that drives the AA onset. Wistar rats were injected with Complete Freund’s Adjuvant (CFA) or saline solution in the hind paws’ footpads and euthanized at 24 or 48 h for genetic and histological analyses. Microarrays revealed the differentially expressed genes between the groups. The CFA dysregulated RA-linked biological processes at both times. Genes of MAPK, Jak-STAT, HIF, PI3K-Akt, TLR, TNF, and NF-κB signaling pathways were altered 24 h before the arrival of immune cells (CD4, CD8, and CD68). Key markers TNF-α, IL-1β, IL-6, NFκB, MEK-1, JAK3, Enolase, and VEGF were immunodetected in fibroblast in CFA-injected footpads at 24 h but not in the control group. Moreover, fibroblasts in the CFA inoculation site overexpressed cadherin-11, which is linked to the migration and invasion ability of RA-FLS. Our study shows that CFA induced a pathological phenotype in the fibroblast of the inoculation site at very early AA stages from 24 h, suggesting a prominent role in arthritis activation processes. © 2023 by the authors. |
| Keywords: | vasculotropin; controlled study; protein expression; nonhuman; phenotype; animal; metabolism; animals; animal tissue; reverse transcription polymerase chain reaction; protein protein interaction; interleukin 1beta; animal experiment; animal model; inflammation; immunoglobulin enhancer binding protein; immunofluorescence; pathology; phosphatidylinositol 3 kinase; histology; mycobacterium tuberculosis; microarray analysis; nf-kappa b; rat; foot pad; interleukin 6; cell migration; fibroblast; fibroblasts; mitogen activated protein kinase 1; rats; rheumatoid arthritis; rats, wistar; bioinformatics; cadherin; lipid metabolism; immunocompetent cell; rna extraction; tumor necrosis factor; wnt signaling; phosphatidylinositol 3-kinases; freund's adjuvant; synovial membrane; freund adjuvant; synoviocyte; synovium; pi3k/akt signaling; arthritis, rheumatoid; mapk signaling; enolase; epifluorescence microscopy; male; article; wistar rat; collagen type 6; differential gene expression; tlr signaling; arthritis, experimental; jak-stat signaling; nf kb signaling; synoviocytes; cadherin-11; fibroblast migration; fibroblast-like synoviocytes; type vi collagen; adjuvant arthritis; hind paw; tnf signaling; experimental arthritis |
| Journal Title: | Cells |
| Volume: | 12 |
| Issue: | 6 |
| ISSN: | 2073-4409 |
| Publisher: | MDPI |
| Date Published: | 2023-03-02 |
| Start Page: | 842 |
| Language: | English |
| DOI: | 10.3390/cells12060842 |
| PUBMED: | 36980183 |
| PROVIDER: | scopus |
| PMCID: | PMC10047124 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2023 -- Source: Scopus |
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