JAK-STAT通路基因在体内类风湿性关节炎模型中的修饰表达：一项探索遗传学见解的临床前研究

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-11 DOI:10.1016/j.bbadis.2025.167780

Maham Ghouri , Nadir Naveed Siddiqui , Mehreen Lateef , Lubna Avesi , Rizma Khan , Humaira Ghauri , Ehtisham Asif , Sitwat Zehra

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引用次数: 0

摘要

背景类风湿性关节炎（RA）是一种慢性炎症性疾病，其特征是滑膜组织炎症、关节恶化和对关节以外系统的影响。该疾病进展的生物学过程尚不清楚，但细胞介导的免疫在RA的发病中起着重要作用。本研究探讨了JAK-STAT通路基因（JAK-1、IL-6和SOCS-2）在类风湿关节炎发病中的作用。方法选取雄性白化Wistar大鼠30只，分为三组。采用AIA（佐剂诱导动物）模型研究疾病的发病机制。采用ELISA法检测血红素和伊红（H和E）， RT-q-PCR法检测表达量。所得数据采用单因素方差分析（ANOVA）进行分析。结果病理证实病变组损伤严重，表现为慢性炎症及软骨退行性改变。此外，小梁间区也可见慢性炎症。RA组JAK1、IL-6、TYK-2水平显著升高。基因表达评估表明，疾病组中JAK-1和IL-6的高表达与RA的进一步发展有关。SOSC2 （JAK-STAT通路的负调节因子）显著(p <；0.01)表达下调。此外，SOCS2可能无法抑制相关jak （IL-6和JAK-1）的转录，导致免疫介质不断释放，参与RA的病理生理。结论JAK-STAT通路可作为炎性和自身免疫性疾病（RA）的诊断和治疗靶点。通过研究JAK-STAT通路基因作为进行性类风湿关节炎治疗候选者的可能意义，该发现可能增加治疗的可能性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

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

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.

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.