We have previously found that β-elemene could inhibit the viability of airway granulation fibroblasts and prevent airway hyperplastic stenosis. This study aimed to elucidate the underlying mechanism and protective efficacy of β-elemene in vitro and in vivo. Microarray and bioinformatic analysis were used to identify altered pathways related to cell viability in a β-elemene-treated primary cell model and to construct a β-elemene-altered ceRNA network modulating the target pathway. Loss of function and gain of function approaches were performed to examine the role of the ceRNA axis in β-elemene's regulation of the target pathway and cell viability. Additionally, in a β-elemene-treated rabbit model of airway stenosis, endoscopic and histological examinations were used to evaluate its therapeutic efficacy and further verify its mechanism of action. The hyperactive ILK/Akt pathway and dysregulated LncRNA-MIR143HG, which acted as a miR-1275 ceRNA to modulate ILK expression, were suppressed in β-elemene-treated airway granulation fibroblasts; β-elemene suppressed the ILK/Akt pathway via the MIR143HG/miR-1275/ILK axis. Additionally, the cell cycle and apoptotic phenotypes of granulation fibroblasts were altered, consistent with ILK/Akt pathway activity. In vivo application of β-elemene attenuated airway granulation hyperplasia and alleviated scar stricture, and histological detections suggested that β-elemene's effects on the MIR143HG/miR-1275/ILK axis and ILK/Akt pathway were in line with in vitro findings. MIR143HG and ILK may act as ceRNA to sponge miR-1275. The MIR143HG/miR-1275/ILK axis mediates β-elemene-induced cell cycle arrest and apoptosis of airway granulation fibroblasts by modulating the ILK/Akt pathway, thereby inhibiting airway granulation proliferation and ultimately alleviating airway stenosis.

中文翻译：

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β-榄香烯通过 MIR143HG 海绵 miR-1275 调节的 ILK/Akt 通路缓解气道狭窄

我们之前已经发现β-榄香烯可以抑制气道肉芽成纤维细胞的活力，防止气道增生性狭窄。本研究旨在阐明β-榄香烯在体外和体内的潜在机制和保护功效。微阵列和生物信息学分析用于在 β-榄香烯处理的原代细胞模型中鉴定与细胞活力相关的改变途径，并构建一个 β-榄香烯改变的 ceRNA 网络来调节目标途径。执行功能丧失和功能获得方法以检查 ceRNA 轴在 β-榄香烯对靶标通路和细胞活力的调节中的作用。此外，在经β-榄香烯处理的气道狭窄兔模型中，通过内窥镜和组织学检查来评估其治疗效果并进一步验证其作用机制。过度活跃的 ILK/Akt 通路和失调的 LncRNA-MIR143HG（作为 miR-1275 ceRNA 调节 ILK 表达）在 β-榄香烯处理的气道肉芽成纤维细胞中受到抑制；β-榄香烯通过 MIR143HG/miR-1275/ILK 轴抑制 ILK/Akt 通路。此外，肉芽成纤维细胞的细胞周期和凋亡表型发生改变，与 ILK/Akt 通路活性一致。β-榄香烯的体内应用减弱了气道肉芽增生并减轻了瘢痕狭窄，组织学检测表明β-榄香烯对MIR143HG/miR-1275/ILK轴和ILK/Akt通路的影响与体外研究结果一致。MIR143HG 和 ILK 可以作为 ceRNA 海绵 miR-1275。