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Piezo1 调控转化生长因子-β1 诱导的慢性鼻-鼻窦炎伴鼻息肉中的上皮-间质转化。

Piezo1 regulates TGF-β1 induced epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps.

机构信息

Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, China.

Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, China.

出版信息

Mol Immunol. 2024 Nov;175:63-73. doi: 10.1016/j.molimm.2024.09.004. Epub 2024 Sep 20.

DOI:10.1016/j.molimm.2024.09.004
PMID:39305849
Abstract

BACKGROUND

Epithelial-mesenchymal transition (EMT) is involved in local tissue remodeling in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the function of Piezo1 in EMT process remains unclear. This study aimed to characterize potential roles of Piezo1 in EMT process in CRSwNP.

METHODS

Overall, 22 nasal polyp (NP) tissues from patients with CRSwNP and 20 middle turbinate from healthy individuals were obtained during surgery. The expression of Piezo1, E-cadherin, vimentin, and α-smooth muscle actin (α-SMA) was measured by using western blot (Wb) in NP tissues and primary human nasal epithelial cells (pHNECs) and the location and level were assessed by immunofluorescence staining. BEAS-2B cells were stimulated with transforming growth factor (TGF)-β1 to induce EMT in vitro model and examined using qRT-PCR. BEAS-2B cells were treated with Yoda1 and RuR to calculate protein level by Wb analysis. Yoda1 and RuR treated NP murine model was evaluated by H&E (hematoxylin-eosin) staining and immunohistochemistry.

RESULTS

Compared with the control group, E-cadherin was decreased while the level of Piezo1, vimentin, and α-SMA was increased in NP group. Piezo1, vimentin, and α-SMA were upregulated in TGF-β1-induced BEAS-2B cells. Yoda1 inhibited E-cadherin expression and promoted Piezo1 and the aforementioned mesenchymal markers, whereas RuR showed contrary results. The results from the murine model treated with Yoda1 and RuR were consistent with those results in the EMT model in vitro.

CONCLUSION

Piezo1 is linked with EMT process in CRSwNP and the activation of Piezo1 exacerbates EMT process of nasal polyps.

摘要

背景

上皮-间充质转化(EMT)参与慢性鼻鼻窦炎伴鼻息肉(CRSwNP)中的局部组织重塑。然而,Piezo1 在 EMT 过程中的功能尚不清楚。本研究旨在探讨 Piezo1 在 CRSwNP 中 EMT 过程中的潜在作用。

方法

本研究共收集了 22 例 CRSwNP 患者的鼻息肉(NP)组织和 20 例健康个体的中鼻甲组织,通过 Western blot(Wb)检测 NP 组织和原代人鼻上皮细胞(pHNECs)中 Piezo1、E-钙黏蛋白、波形蛋白和α-平滑肌肌动蛋白(α-SMA)的表达,免疫荧光染色评估其定位和水平。体外采用转化生长因子(TGF)-β1 刺激 BEAS-2B 细胞建立 EMT 模型,并进行 qRT-PCR 检测。通过 Wb 分析计算 Yoda1 和 RuR 处理后细胞的蛋白水平。通过 H&E(苏木精-伊红)染色和免疫组化评估 Yoda1 和 RuR 处理的 NP 鼠模型。

结果

与对照组相比,NP 组中 E-钙黏蛋白降低,Piezo1、波形蛋白和α-SMA 水平升高。TGF-β1 诱导的 BEAS-2B 细胞中 Piezo1、波形蛋白和α-SMA 表达上调。Yoda1 抑制 E-钙黏蛋白表达并促进 Piezo1 和上述间充质标志物表达,而 RuR 则呈现相反的结果。Yoda1 和 RuR 处理的鼠模型结果与体外 EMT 模型结果一致。

结论

Piezo1 与 CRSwNP 中的 EMT 过程有关,Piezo1 的激活可加重鼻息肉的 EMT 过程。

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