Ceapin-A7 counteracts the protective effects of Lanreotide in endothelial cells

Aspects of molecular medicine Pub Date : 2026-06-01 Epub Date: 2026-03-03 DOI:10.1016/j.amolm.2026.100104

Md Matiur Rahman Sarker, Saikat Fakir, Madan Sigdel, Nektarios Barabutis

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Abstract

Background

Pulmonary endothelial barrier dysfunction is characterized by increased vascular permeability, lung edema, and impaired gas exchange. Synthetic somatostatin analogs (SSA), including Lanreotide (LAN), have demonstrated cytoprotective effects in experimental models of endothelial injury, but the corresponding mechanisms mediating those effects are still unclear.

Objective

This study aimed to determine whether the unfolded protein response (UPR) sensor ATF6 is involved in the protective outcomes of LAN in lung endothelial cells.

Methods

Human and bovine pulmonary endothelial cells were exposed to Ceapin-A7, an ATF6 inhibitor, prior to LAN exposure. Protein expression levels of BiP, Grp94, MLC2, Cofilin, STAT1, STAT3, and stress kinases were assessed. Reactive oxygen species (ROS) generation was also measured, as well as paracellular permeability using FITC-Dextran assay.

Results

LAN enhanced protein expression of BiP and Grp94, decreased ROS production, suppressed STAT1, STAT3 and ERK1/2 phosphorylation, and improved barrier function. Those effects were counteracted by Ceapin-A7.

Conclusions

Our findings suggest that ATF6 inhibition opposes the beneficial effects of LAN in endothelial cells.

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Ceapin-A7抵消Lanreotide对内皮细胞的保护作用

肺内皮屏障功能障碍的特征是血管通透性增加、肺水肿和气体交换受损。合成的生长抑素类似物（SSA），包括Lanreotide (LAN)，已经在内皮损伤的实验模型中显示出细胞保护作用，但介导这些作用的相应机制尚不清楚。目的探讨未折叠蛋白反应（UPR）传感器ATF6是否参与LAN对肺内皮细胞的保护作用。方法将人类和牛肺内皮细胞暴露于一种ATF6抑制剂Ceapin-A7中，然后再暴露于LAN中。评估BiP、Grp94、MLC2、Cofilin、STAT1、STAT3和应激激酶的蛋白表达水平。还测量了活性氧（ROS）的产生，以及使用fitc -葡聚糖测定细胞旁通透性。结果slan提高了BiP和Grp94蛋白的表达，减少了ROS的产生，抑制了STAT1、STAT3和ERK1/2的磷酸化，改善了屏障功能。这些影响被Ceapin-A7抵消。结论ATF6的抑制作用与LAN对内皮细胞的有益作用相反。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aspects of molecular medicine Molecular Biology, Molecular Medicine

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审稿时长

38 days