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BAFF 与狼疮肾炎中 PI3K/Akt/mTOR 信号的关联。

Association of BAFF with PI3K/Akt/mTOR signaling in lupus nephritis.

机构信息

Department of Rheumatology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):5793-5798. doi: 10.3892/mmr.2017.7367. Epub 2017 Aug 28.

Abstract

Systemic lupus erythematosus is a connective tissue disease characterized by autoimmune inflammation, which leads to specific and nonspecific immune disorders with the formation of various autoantibodies by activated B cells. B‑cell‑activating factor (BAFF) is secreted by macrophages and activated T cells, and is responsible for the proliferation, maturation and differentiation of B cells. However, the mechanism of BAFF involvement in lupus nephritis (LN) remains unclear. The aim of the present study was to investigate the association between BAFF and phosphoinositide 3‑kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling in order to elucidate the pathogenesis of LN. In the present study, 18 patients with LN and 20 controls were included. The clinical data were analyzed and plasma levels of BAFF were measured using an ELISA. The mRNA and protein levels of BAFF, phosphorylated (p)‑PI3K, p‑Akt and p‑mTOR in kidney tissues were measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting. Plasma BAFF levels were significantly increased in patients with LN compared with the controls (P<0.001). mRNA and protein levels of BAFF, p‑PI3K, p‑Akt and p‑mTOR in kidney tissue were significantly increased in patients with LN compared with the controls (all P<0.001). mRNA and protein levels of BAFF in the kidney tissues of patients with LN were positively correlated with the levels of p‑PI3K, p‑Akt and p‑mTOR. The results of the present study revealed a correlation between BAFF and the PI3K/Akt/mTOR signaling pathway, and it is hypothesized that they are involved in the pathogenesis of LN.

摘要

系统性红斑狼疮是一种以自身免疫炎症为特征的结缔组织疾病,它导致特定和非特定的免疫紊乱,从而导致激活的 B 细胞形成各种自身抗体。B 细胞激活因子(BAFF)由巨噬细胞和活化的 T 细胞分泌,负责 B 细胞的增殖、成熟和分化。然而,BAFF 参与狼疮性肾炎(LN)的机制尚不清楚。本研究旨在探讨 BAFF 与磷脂酰肌醇 3-激酶/蛋白激酶 B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路之间的关系,以阐明 LN 的发病机制。本研究纳入了 18 例 LN 患者和 20 例对照者。分析了临床资料,并采用酶联免疫吸附试验(ELISA)测定了血浆 BAFF 水平。采用逆转录-定量聚合酶链反应(RT-qPCR)和蛋白质印迹法测定了肾组织中 BAFF、磷酸化(p)-PI3K、p-Akt 和 p-mTOR 的 mRNA 和蛋白水平。与对照组相比,LN 患者的血浆 BAFF 水平显著升高(P<0.001)。与对照组相比,LN 患者肾组织中 BAFF、p-PI3K、p-Akt 和 p-mTOR 的 mRNA 和蛋白水平均显著升高(均 P<0.001)。LN 患者肾组织中 BAFF 的 mRNA 和蛋白水平与 p-PI3K、p-Akt 和 p-mTOR 的水平呈正相关。本研究结果表明,BAFF 与 PI3K/Akt/mTOR 信号通路之间存在相关性,推测它们参与了 LN 的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd15/5865758/2c5865569355/mmr-16-05-5793-g00.jpg

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