TSLP通过TGF-β1/Smad2/3信号传导诱导过敏性鼻炎患者鼻上皮细胞的上皮-间质转化。

IF 2.5 3区 医学 Q1 OTORHINOLARYNGOLOGY American Journal of Rhinology & Allergy Pub Date : 2023-11-01 Epub Date: 2023-08-03 DOI:10.1177/19458924231193154
Hong Wei Yu, Wei Wei Wang, Qian Jing, Yong Liang Pan
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引用次数: 1

摘要

背景:亚洲过敏性鼻炎(AR)患者的气道重塑得到证实。上皮-间充质转化(EMT)是气道重塑的关键机制之一。胸腺基质淋巴细胞生成素(TSLP)是气道重塑的重要因素。尽管在AR中发现TSLP增加,但人们对TSLP是否通过诱导EMT参与气道重塑知之甚少。目的:研究TSLP对AR患者人鼻上皮细胞(HNEC)EMT的影响。方法:在不存在或存在转化生长因子β1(TGF-β1)受体选择性抑制剂(SB431542)的情况下,用TSLP刺激AR患者的人鼻上皮细胞。采用实时聚合酶链反应、蛋白质印迹和免疫细胞化学方法评估TGF-β1在细胞中的表达。Western印迹和免疫细胞化学用于检测细胞中的EMT标记物,包括波形蛋白、成纤维细胞特异性蛋白1(FSP1)和E-钙粘蛋白、针对脑脊髓瘫痪同源物2/3(Smad2/3)的小母亲以及磷酸化的Smad2/3。通过酶联免疫测定测定上清液中细胞外基质成分如胶原I和III的水平。倒置相差显微镜下观察细胞形态变化。结果:TSLP刺激后TGF-β1mRNA和蛋白呈浓度依赖性增加。此外,TSLP降低了E-钙粘蛋白的表达,但上调了FSP1和波形蛋白的产生,同时增加了胶原I和III的水平,细胞的形态转变为成纤维细胞样形状。此外,发现Smad2/3蛋白的磷酸化显著增加。然而,SB431542预培养逆转了这些作用。结论:TSLP通过TGF-β1介导的Smad2/3激活诱导HNECs经历EMT过程。TSLP是HNEC中EMT的激活剂,可能是抑制AR中EMT和减少气道重塑的潜在靶点。
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TSLP Induces Epithelial-Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-β1/Smad2/3 Signaling.

Background: Airway remodeling is demonstrated in Asian patients with allergic rhinitis (AR). The epithelial-mesenchymal transition (EMT) is one of the key mechanisms underlying airway remodeling. Thymic stromal lymphopoietin (TSLP) is an important contributor to airway remodeling. Although increased TSLP is found in AR, little is known about whether TSLP is involved in airway remodeling through induction of the EMT.

Objective: We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients.

Methods: Human nasal epithelial cells from AR patients were stimulated with TSLP in the absence or presence of the preincubation with a selective inhibitor of transforming growth factor beta 1 (TGF-β1) receptor (SB431542). The expression of TGF-β1 in the cells was evaluated by using real-time polymerase chain reaction, Western blotting, and immunocytochemistry. Western blotting and immunocytochemistry were used to assay EMT markers including vimentin, fibroblast-specific protein 1 (FSP1) and E-cadherin, small mothers against decapentaplegic homolog2/3 (Smad2/3), and phosphorylated Smad2/3 in the cells. The levels of extracellular matrix components such as collagens I and III in supernatants were measured by enzyme-linked immunoassay. Morphological changes of the cells were observed under inverted phase-contrast microscope.

Results: A concentration-dependent increase of TGF-β1 mRNA and protein was observed following stimulation with TSLP. Furthermore, TSLP decreased the expression of E-cadherin protein, but upregulated the production of FSP1 and vimentin proteins along with increased levels of collagens I and III, and the morphology of the cells was transformed into fibroblast-like shape. Additionally, a significant increase was found in phosphorylation of Smad2/3 protein. However, these effects were reversed by SB431542 preincubation.

Conclusion: TSLP-induced HNECs to undergo the EMT process via TGF-β1-mediated Smad2/3 activation. TSLP is an activator of the EMT in HNECs and might be a potential target for inhibiting EMT and reducing airway remodeling in AR.

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来源期刊
CiteScore
5.60
自引率
11.50%
发文量
82
审稿时长
4-8 weeks
期刊介绍: The American Journal of Rhinology & Allergy is a peer-reviewed, scientific publication committed to expanding knowledge and publishing the best clinical and basic research within the fields of Rhinology & Allergy. Its focus is to publish information which contributes to improved quality of care for patients with nasal and sinus disorders. Its primary readership consists of otolaryngologists, allergists, and plastic surgeons. Published material includes peer-reviewed original research, clinical trials, and review articles.
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