Lu Zou, Xiao Yu, Ling Tang, Chunrong Guo, Zhumei Sun, Shaobin Li, Yanqi Cheng, Fufeng Li, Hong Fang
{"title":"针对哮喘气道重塑：宣肺平喘方通过tgf - β1/Smad通路调节的抗emt作用","authors":"Lu Zou, Xiao Yu, Ling Tang, Chunrong Guo, Zhumei Sun, Shaobin Li, Yanqi Cheng, Fufeng Li, Hong Fang","doi":"10.2174/0118761429360075250320062131","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Asthma is a chronic airway disease characterized by Airway Remodeling (AR) and persistent inflammation, with Epithelial-Mesenchymal Transition (EMT) playing a crucial role in fibrosis and smooth muscle proliferation. The Transforming Growth Factor-Beta1 (TGFβ1)/Smad pathway is a key driver of EMT in asthma. Current treatments do not effectively prevent AR progression. Traditional Chinese Medicine, particularly the Xuanfei Pingchuan (XFPC) prescription, has shown potential in managing asthma, but its role in EMT regulation remains unclear.</p><p><strong>Methods: </strong>This study explored the role of \"phlegm and stasis\" in airway remodeling (AR) in asthma from the perspective of EMT and investigated the effects and underlying mechanisms of XFPC prescription on EMT in AR. <i>In vitro</i>, human bronchial epithelial (16HBE) cells were induced into EMT with TGFβ1 and treated with XFPC drug-containing serum, with EMT marker expression analyzed <i>via</i> RT-qPCR and Western blot. <i>In vivo</i>, an ovalbumin (OVA)-induced asthma model in Sprague Dawley rats was used to evaluate the effects of different XFPC doses through histopathology, immunofluorescence, and molecular analyses. Additionally, Smurf2 cDNA transfection was conducted to assess the role of Smurf2 in EMT regulation.</p><p><strong>Results: </strong>The results confirmed that XFPC prescription suppressed the pathway of transforming-growth factor-beta1 (TGFβ1)-Smad by reducing Smad ubiquitination regulator 2 (Smurf2), Smad2, Smad3, TGFβ1 receptor (TβRI), N-cadherin, α-SMA, and Vimentin in terms of expressions at messenger ribonucleic acid (mRNA) and protein levels. However, XFPC prescription up-regulated expressions of SnoN and E-cadherin at protein and mRNA levels to inhibit EMT. The result also confirmed that XFPC prescription decreased the ubiquitination of Smad7.</p><p><strong>Conclusion: </strong>XFPC prescription could suppress AR in TGFβ1 induced 16HBE cells and OVA-sensitized animal models through TGFβ1/Smad pathway.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e18761429360075"},"PeriodicalIF":2.9000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeting Airway Remodeling in Asthma: Anti-EMT Effects of Xuanfei Pingchuan Prescription <i>via</i> TGFβ1/Smad Pathway Modulation.\",\"authors\":\"Lu Zou, Xiao Yu, Ling Tang, Chunrong Guo, Zhumei Sun, Shaobin Li, Yanqi Cheng, Fufeng Li, Hong Fang\",\"doi\":\"10.2174/0118761429360075250320062131\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Asthma is a chronic airway disease characterized by Airway Remodeling (AR) and persistent inflammation, with Epithelial-Mesenchymal Transition (EMT) playing a crucial role in fibrosis and smooth muscle proliferation. The Transforming Growth Factor-Beta1 (TGFβ1)/Smad pathway is a key driver of EMT in asthma. Current treatments do not effectively prevent AR progression. Traditional Chinese Medicine, particularly the Xuanfei Pingchuan (XFPC) prescription, has shown potential in managing asthma, but its role in EMT regulation remains unclear.</p><p><strong>Methods: </strong>This study explored the role of \\\"phlegm and stasis\\\" in airway remodeling (AR) in asthma from the perspective of EMT and investigated the effects and underlying mechanisms of XFPC prescription on EMT in AR. <i>In vitro</i>, human bronchial epithelial (16HBE) cells were induced into EMT with TGFβ1 and treated with XFPC drug-containing serum, with EMT marker expression analyzed <i>via</i> RT-qPCR and Western blot. <i>In vivo</i>, an ovalbumin (OVA)-induced asthma model in Sprague Dawley rats was used to evaluate the effects of different XFPC doses through histopathology, immunofluorescence, and molecular analyses. Additionally, Smurf2 cDNA transfection was conducted to assess the role of Smurf2 in EMT regulation.</p><p><strong>Results: </strong>The results confirmed that XFPC prescription suppressed the pathway of transforming-growth factor-beta1 (TGFβ1)-Smad by reducing Smad ubiquitination regulator 2 (Smurf2), Smad2, Smad3, TGFβ1 receptor (TβRI), N-cadherin, α-SMA, and Vimentin in terms of expressions at messenger ribonucleic acid (mRNA) and protein levels. However, XFPC prescription up-regulated expressions of SnoN and E-cadherin at protein and mRNA levels to inhibit EMT. The result also confirmed that XFPC prescription decreased the ubiquitination of Smad7.</p><p><strong>Conclusion: </strong>XFPC prescription could suppress AR in TGFβ1 induced 16HBE cells and OVA-sensitized animal models through TGFβ1/Smad pathway.</p>\",\"PeriodicalId\":93964,\"journal\":{\"name\":\"Current molecular pharmacology\",\"volume\":\"17 \",\"pages\":\"e18761429360075\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current molecular pharmacology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/0118761429360075250320062131\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118761429360075250320062131","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Targeting Airway Remodeling in Asthma: Anti-EMT Effects of Xuanfei Pingchuan Prescription via TGFβ1/Smad Pathway Modulation.
Background: Asthma is a chronic airway disease characterized by Airway Remodeling (AR) and persistent inflammation, with Epithelial-Mesenchymal Transition (EMT) playing a crucial role in fibrosis and smooth muscle proliferation. The Transforming Growth Factor-Beta1 (TGFβ1)/Smad pathway is a key driver of EMT in asthma. Current treatments do not effectively prevent AR progression. Traditional Chinese Medicine, particularly the Xuanfei Pingchuan (XFPC) prescription, has shown potential in managing asthma, but its role in EMT regulation remains unclear.
Methods: This study explored the role of "phlegm and stasis" in airway remodeling (AR) in asthma from the perspective of EMT and investigated the effects and underlying mechanisms of XFPC prescription on EMT in AR. In vitro, human bronchial epithelial (16HBE) cells were induced into EMT with TGFβ1 and treated with XFPC drug-containing serum, with EMT marker expression analyzed via RT-qPCR and Western blot. In vivo, an ovalbumin (OVA)-induced asthma model in Sprague Dawley rats was used to evaluate the effects of different XFPC doses through histopathology, immunofluorescence, and molecular analyses. Additionally, Smurf2 cDNA transfection was conducted to assess the role of Smurf2 in EMT regulation.
Results: The results confirmed that XFPC prescription suppressed the pathway of transforming-growth factor-beta1 (TGFβ1)-Smad by reducing Smad ubiquitination regulator 2 (Smurf2), Smad2, Smad3, TGFβ1 receptor (TβRI), N-cadherin, α-SMA, and Vimentin in terms of expressions at messenger ribonucleic acid (mRNA) and protein levels. However, XFPC prescription up-regulated expressions of SnoN and E-cadherin at protein and mRNA levels to inhibit EMT. The result also confirmed that XFPC prescription decreased the ubiquitination of Smad7.
Conclusion: XFPC prescription could suppress AR in TGFβ1 induced 16HBE cells and OVA-sensitized animal models through TGFβ1/Smad pathway.
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