Hong Wei Yu, Wei Wei Wang, Qian Jing, Yong Liang Pan
{"title":"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。","authors":"Hong Wei Yu, Wei Wei Wang, Qian Jing, Yong Liang Pan","doi":"10.1177/19458924231193154","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":7650,"journal":{"name":"American Journal of Rhinology & Allergy","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"TSLP Induces Epithelial-Mesenchymal Transition in Nasal Epithelial Cells From Allergic Rhinitis Patients Through TGF-β1/Smad2/3 Signaling.\",\"authors\":\"Hong Wei Yu, Wei Wei Wang, Qian Jing, Yong Liang Pan\",\"doi\":\"10.1177/19458924231193154\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We investigated the effect of TSLP on the EMT in human nasal epithelial cells (HNECs) from AR patients.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":7650,\"journal\":{\"name\":\"American Journal of Rhinology & Allergy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Rhinology & Allergy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/19458924231193154\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"OTORHINOLARYNGOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Rhinology & Allergy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/19458924231193154","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"OTORHINOLARYNGOLOGY","Score":null,"Total":0}
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.
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.