Aims

C1q/tumor necrosis factor-related protein-1 (CTRP1) is a newly identified adiponectin paralog that modulates metabolism and inflammation. However, the cerebral function of CTRP1 remains unknown. This study aimed to determine its role and mechanism in cerebral ischemia and reperfusion injury.

Main methods

Serum level of CTRP1 as well as high-sensitivity C reactive protein (hs-CRP) in stroke patients was measured by ELISA assay. The levels of TNF-α, IL-1β, and IL-6 were analyzed using ELISA kits. Quantitative RT-PCR, western blot analysis were conducted to detect indicated genes.

Key findings

CTRP1 was significantly upregulated in sera from patients with stroke and positive correlation with hs-CRP. CTRP1 was significantly upregulated in BV2 microglia exposed to oxygen and glucose deprivation and reperfusion (OGD/R). Knockdown of CTRP1 by si-CTRP1 transfection markedly enhanced OGD/R-induced autophagy and accelerated the inflammatory response in BV2 cells, as indicated by increased expression of LC3-II/LC3-I and beclin1, as well as increased concentration of the proinflammatory cytokines TNF-α, IL-1β, and IL-6. However, recombinant CTRP1 or overexpression of CTRP1 attenuated OGD/R-induced autophagy and inflammatory response in BV2 cells. Further study demonstrated that knockdown of CTRP1 decreased, while recombinant CTRP1 increased the phosphorylation of Akt and mTOR in BV2 cells. IGF-1, which activates PI3-kinase and MEK1/2, abolished the promotive effect of si-CTRP1, while inhibition of Akt with A6730 reversed the inhibitory effect of recombinant CTRP1 on BV2 cells autophagy and inflammation response.

Significance

CTRP1 inhibited microglia autophagy and inflammation response by regulating the Akt/mTOR pathway.

中文翻译：

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C1q /肿瘤坏死因子相关蛋白-1通过调节Akt / mTOR途径减弱小胶质细胞自噬和炎症反应。

目的

C1q /肿瘤坏死因子相关蛋白1（CTRP1）是新发现的脂联素旁系同源物，可调节代谢和炎症。但是，CTRP1的脑功能仍然未知。本研究旨在确定其在脑缺血和再灌注损伤中的作用和机制。

主要方法

通过ELISA法测定中风患者的血清CTRP1以及高敏C反应蛋白（hs-CRP）。使用ELISA试剂盒分析TNF-α，IL-1β和IL-6的水平。进行定量RT-PCR，蛋白质印迹分析以检测指示的基因。

主要发现

中风患者血清中的CTRP1明显上调，并且与hs-CRP呈正相关。在暴露于氧气和葡萄糖剥夺和再灌注（OGD / R）的BV2小胶质细胞中，CTRP1显着上调。si-CTRP1转染可降低CTRP1的表达，可显着增强OGD / R诱导的自噬并加速BV2细胞的炎症反应，如LC3-II / LC3-I和beclin1的表达增加以及促炎细胞因子的浓度增加所表明TNF-α，IL-1β和IL-6。但是，重组CTRP1或CTRP1的过表达减弱了BGD2细胞中OGD / R诱导的自噬和炎症反应。进一步的研究表明，CTRP1的敲低降低，而重组CTRP1增强BV2细胞中Akt和mTOR的磷酸化。IGF-1可激活PI3激酶和MEK1 / 2，

意义

CTRP1通过调节Akt / mTOR途径抑制小胶质细胞自噬和炎症反应。