Interleukin-1 receptor-associated kinase 2 promotes inflammatory reactions by activating the nuclear factor kappa-B signaling pathway in diabetic nephropathy

IF 1.5 4区 医学 Q4 IMMUNOLOGY
Jingjing Liu, Yingying Xu, Shijie Cheng, Chenfang Wang, Zhengyu Zhang
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引用次数: 0

Abstract

Diabetic nephropathy (DN) is a major complication of diabetes. Interleukin-1 receptor-associated kinase 2 (IRAK2) has been implicated in various diseases. This study aimed to investigate the role of IRAK2 in DN progression and its association with inflammation and the nuclear factor-kappa B (NF-κB) signaling pathway. DN model mice were generated by intraperitoneal injection of streptozotocin. IRAK2 expression was upregulated in the DN model mice. IRAK2 knockdown increased weight and reduced blood glucose levels in DN model mice. In addition, IRAK2 downregulation improved glomerular morphology in DN mice. IRAK2 knockdown reduced the levels of kidney damage biomarkers (24-h urinary protein, urine albumin-creatinine ratio, and plasma creatinine) and inflammatory cytokines (IL-6, tumor necrosis factor [TNF]-α, TNF-1R, and TNF-2R). Moreover, IRAK2 activated the NF-κB signaling pathway in DN model mice. Overexpression of NF-κB exacerbated DN progression, and IRAK2 knockdown reversed these effects. IRAK2 promoted DN progression and inflammation by activating the NF-κB signaling pathway. These findings suggest that IRAK2 is a potential therapeutic target for DN treatment.
白细胞介素-1 受体相关激酶 2 通过激活糖尿病肾病的核因子卡巴-B 信号通路促进炎症反应
糖尿病肾病(DN)是糖尿病的主要并发症。白细胞介素-1受体相关激酶2(IRAK2)与多种疾病有关。本研究旨在探讨IRAK2在DN进展中的作用及其与炎症和核因子-卡巴B(NF-κB)信号通路的关系。通过腹腔注射链脲佐菌素产生了 DN 模型小鼠。IRAK2在DN模型小鼠中表达上调。敲除 IRAK2 可增加 DN 模型小鼠的体重并降低血糖水平。此外,IRAK2 下调还改善了 DN 模型小鼠的肾小球形态。IRAK2 下调降低了肾损伤生物标志物(24 小时尿蛋白、尿白蛋白-肌酐比值和血浆肌酐)和炎症细胞因子(IL-6、肿瘤坏死因子 [TNF]-α、TNF-1R 和 TNF-2R)的水平。此外,IRAK2 还激活了 DN 模型小鼠的 NF-κB 信号通路。NF-κB的过度表达加剧了DN的进展,而IRAK2的敲除则逆转了这些影响。IRAK2通过激活NF-κB信号通路促进了DN的进展和炎症。这些发现表明,IRAK2是治疗DN的潜在治疗靶点。
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来源期刊
CiteScore
3.00
自引率
0.00%
发文量
17
审稿时长
6-12 weeks
期刊介绍: Central European Journal of Immunology is a English-language quarterly aimed mainly at immunologists.
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