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锌指蛋白转录因子16通过调节缺氧诱导因子-1α通路在类风湿关节炎中发挥抗血管生成作用。

ZBTB16 exerts anti-angiogenic effects in rheumatoid arthritis by regulating HIF-1α pathway.

作者信息

Chen Xueqin, Liu Yongmei, Xia Jiangli, Ma Xixi, Hu Linwei

机构信息

Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China;

Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

出版信息

Allergol Immunopathol (Madr). 2025 Jul 1;53(4):85-92. doi: 10.15586/aei.v53i4.1270. eCollection 2025.

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is one complex chronic autoimmune disease, resulting body pain and badly affect the health of RA patients. Zinc finger and BTB domain containing 16 (ZBTB16) has been reported to participate into many diseases including osteoarthritis and osteoporosis.

OBJECTIVE

To verify the regulatory functions of ZBTB16 in RA progression keep dimness.

METHODS

The mRNA expressions were tested through RT-qPCR. The protein expressions were evaluated through western blot. The pathological changes of synovial tissues were determined through HE staining. The erosion and destruction of bone tissues were examined through safranin-O/fast green staining. The levels of TNF-α, IL-1β, IL-6 and MMP-3 were testified through ELISA. The fluorescence intensity of proteins was assessed through IF assay.

RESULTS

Firstly, it was uncovered that ZBTB16 expression was markedly reduced in the synovium tissues of RA patients through analyzing GSE55235 expression profile by GEO2R online tool. Next, ZBTB16 expression was down-regulated in synovial tissues of RA patients. Moreover, ZBTB16 can alleviate the degree of paw swelling in CIA mice. ZBTB16 improved the pathological changes of synovial tissues in CIA mice. The levels of inflammatory factors and matrix metalloproteinase were increased in CIA mice, but these impacts were reversed after ZBTB16 amplification. ZBTB16 can relieve pannus in CIA mice. Besides, the triggered GRK2/HIF-1α pathway in CIA mice can be retarded after ZBTB16 overexpression.

CONCLUSION

ZBTB16 exerted anti-angiogenic effects in RA by blocking GRK2/HIF-1α pathway. This work hinted that ZBTB16 may be one useful target for RA treatment.

摘要

背景

类风湿关节炎(RA)是一种复杂的慢性自身免疫性疾病,会导致身体疼痛,严重影响RA患者的健康。据报道,含锌指和BTB结构域蛋白16(ZBTB16)参与包括骨关节炎和骨质疏松症在内的多种疾病。

目的

验证ZBTB16在RA进展中的调控作用尚不清楚。

方法

通过RT-qPCR检测mRNA表达。通过蛋白质印迹法评估蛋白质表达。通过HE染色确定滑膜组织的病理变化。通过番红O/固绿染色检查骨组织的侵蚀和破坏情况。通过ELISA检测TNF-α、IL-1β、IL-6和MMP-3的水平。通过免疫荧光法评估蛋白质的荧光强度。

结果

首先,通过GEO2R在线工具分析GSE55235表达谱发现,RA患者滑膜组织中ZBTB16表达明显降低。其次,RA患者滑膜组织中ZBTB16表达下调。此外,ZBTB16可减轻胶原诱导性关节炎(CIA)小鼠的爪肿胀程度。ZBTB16改善了CIA小鼠滑膜组织的病理变化。CIA小鼠炎症因子和基质金属蛋白酶水平升高,但ZBTB16扩增后这些影响得到逆转。ZBTB16可减轻CIA小鼠的血管翳。此外,ZBTB16过表达后可抑制CIA小鼠中触发的GRK2/HIF-1α通路。

结论

ZBTB16通过阻断GRK2/HIF-1α通路在RA中发挥抗血管生成作用。这项研究提示ZBTB16可能是RA治疗的一个有效靶点。

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