The Wnt7b/β-catenin signaling pathway is involved in the protective action of calcitonin gene-related peptide on hyperoxia-induced lung injury in premature rats.

The Wnt7b/β-catenin signaling pathway is involved in the protective action of calcitonin gene-related peptide on hyperoxia-induced lung injury in premature rats.
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Wnt7b/β-catenin信号通路参与降钙素基因相关肽对早产大鼠高氧诱导的肺损伤的保护作用。

DOI:
10.1186/s11658-018-0071-7
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发表时间:
2018
影响因子:
8.3
通讯作者:
Zheng X
Zheng X
中科院分区:
生物学1区
文献类型:
--
作者:
Wang S;Dang H;Xu F;Deng J;Zheng X

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降钙素基因相关肽(CGRP)可以预防高氧引起的肺损伤,使得 CGRP 的上调成为此类损伤的潜在治疗方法。然而,CGRP 对 Wnt7b/β-catenin 信号通路的影响尚不清楚。在本研究中,我们研究了 CGRP 和 Wnt7b/β-catenin 信号通路在高氧诱导的肺损伤中的作用。早产儿 Sprague Dawley (SD) 大鼠分别暴露于 21%、40%、60% 和 95% 的氧气中 3、7 和 14 天。测量动物的体重、存活率和内源性 CGRP 水平。采集肺样本进行组织学分析并测量丙二醛(MDA)浓度和总抗氧化能力(TAOC)。我们还评估了给予 200 nmol/kg CGRP8-37(一种 CGRP 拮抗剂)后肺组织中的 MDA 浓度和 TAOC。最后,从早产大鼠中分离出 II 型肺泡上皮细胞 (AEC II),将其暴露于 21% 或 95% 的氧气中 3、7 和 14 天,并用 10− 8 mol/l 外源 CGRP 处理。使用蛋白质印迹评估Wnt7b和β-连环蛋白的蛋白表达,并使用qPCR评估TCF和c-myc mRNA表达。暴露于 60% 和 95% 氧气的老鼠的体重和存活率显着低于 21% 和 40% 氧气组,并且这种下降是时间依赖性的。暴露于 95% 氧气的早产大鼠肺组织中内源性 CGRP 升高。 CGRP8-37 诱导肺组织明显炎症和肺泡结构重塑。此外,暴露 3 天后,Wnt7b 和 β-catenin 的表达水平显着增加。它们在 7 天时达到顶峰,然后在 14 天时下降。与仅经历高氧的细胞相比,CGRP 处理后 AEC II 细胞中的 TCF/c-myc 水平显着增加。 CGRP 可保护早产大鼠免受高氧诱导的肺损伤。该过程涉及 Wnt7b/β-catenin 信号通路。
Calcitonin gene-related peptide (CGRP) can protect against hyperoxia-induced lung injury, making the upregulation of CGRP a potential therapeutic approach for this type of injury. However, the effects of CGRP on the Wnt7b/β-catenin signaling pathway are unclear. In this study, we investigated the roles of CGRP and the Wnt7b/β-catenin signaling pathway in hyperoxia-induced lung injury. Premature Sprague Dawley (SD) rats were exposed to 21, 40, 60 and 95% oxygen for 3, 7 and 14 days. The animals’ body weights, survival rates and endogenous CGRP levels were measured. Lung samples were harvested for histological analyses and measurements of malondialdehyde (MDA) concentration and total antioxidant capacity (TAOC). We also assessed the MDA concentration and TAOC in the lung tissues after administration of 200 nmol/kg CGRP8–37 (a CGRP antagonist). Finally, alveolar epithelial type II (AEC II) cells were isolated from premature rats, exposed to 21 or 95% oxygen for 3, 7 and 14 days, and treated with 10− 8 mol/l exogenous CGRP. The protein expressions of Wnt7b and β-catenin were assessed using western blotting, and TCF and c-myc mRNA expressions were assessed using qPCR. Rats exposed to 60 and 95% oxygen had significantly lower body weights and survival rates than the 21 and 40% groups, and the decrease was time dependent. Endogenous CGRP was elevated in the lung tissues of premature rats exposed to 95% oxygen. CGRP8–37 induced apparent inflammation in the lung tissue and alveolar structural remodeling. In addition, the expression levels of Wnt7b and β-catenin were markedly increased after exposure for 3 days. They peaked at 7 days, then declined at 14 days. The levels of TCF/c-myc in AEC II cells increased significantly after CGRP treatment when compared with cells that had only undergone hyperoxia. CGRP protected against hyperoxia-induced lung injury in premature rats. This process involves the Wnt7b/β-catenin signaling pathway.
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