Modified expression of JAK-STAT pathway genes in an in vivo rheumatoid arthritis model: A preclinical study to explore genetic insights

Abstract

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by inflammatory synovial tissue, joint deterioration, and effects on systems other than the joints. The biological process underlying the progression of the disease remains unknown, however cell-mediated immunity plays an important part in the onset of RA. The current study investigated the involvement of the JAK-STAT pathway genes (JAK-1, IL-6, and SOCS-2) in the pathogenesis of RA (Rheumatoid arthritis).

Methodology: The study was carried out on thirty male Albino Wistar rats categorised in to the three groups. The AIA (Adjuvant induced animal) model was utilised to study the disease pathogenesis. The haematoxylin and Eosin (H and E) was performed followed by ELISA and expression analyses by RT-q-PCR. The obtained data was analysed using one-way ANOVA (Analysis of Variance).

Results: Histopathology confirmed that diseased group appeared to be severely impaired, demonstrating manifestations of inflammation with chronic as well as cartilage degenerative changes. Furthermore, chronic inflammation was also noticed in the intertrabecular area. The significant increased levels of JAK1, IL-6 and TYK-2 were recorded among RA group. The gene expression assessment indicated that higher expression of JAK-1 and IL-6 was linked to the further development of RA in the disease group. The SOSC2 (a negative regulator of the JAK-STAT pathway) was significantly (p < 0.01) downregulated. Moreover, SOCS2 may be unable to suppress the transcription of the related JAKs (IL-6 and JAK-1), resulting in the constant release of immune mediators and contributing to the pathophysiology of RA.

Conclusions: The JAK-STAT pathway may serve as the target for diagnosing and treating inflammatory and autoimmune disorders (RA). The findings may enhance therapeutic possibilities by investigating the possible implications of JAK-STAT pathway genes as candidates for progressive rheumatoid arthritis therapies.

Keywords: Bone degeneration; Gene expression; Histopathology; Inflammation; Intertrabecular area; Janus Kinase; Quality of life.