Interleukin-9 promotes EMT-mediated PM2.5-induced pulmonary fibrosis by activating the STAT3 pathway

IF 4.8 2区 医学 Q1 TOXICOLOGY
Yuxuan Li, Yi Zhong, Chenwen Li, Zhixia Han, Yan Cui, Renjiang He, Yingyi Liu, Qinlin Cui, Daping He, Zhengquan Hu, Qingbi Zhang, Jun Bai
{"title":"Interleukin-9 promotes EMT-mediated PM2.5-induced pulmonary fibrosis by activating the STAT3 pathway","authors":"Yuxuan Li,&nbsp;Yi Zhong,&nbsp;Chenwen Li,&nbsp;Zhixia Han,&nbsp;Yan Cui,&nbsp;Renjiang He,&nbsp;Yingyi Liu,&nbsp;Qinlin Cui,&nbsp;Daping He,&nbsp;Zhengquan Hu,&nbsp;Qingbi Zhang,&nbsp;Jun Bai","doi":"10.1007/s00204-024-03864-6","DOIUrl":null,"url":null,"abstract":"<div><p>This study investigated the impact of PM<sub>2.5</sub> on promoting EMT in PM<sub>2.5</sub>-induced pulmonary fibrosis (PF) development and explored molecular mechanisms of the IL-9/STAT3/Snail/TWIST1 signaling pathway in PF owing to PM<sub>2.5</sub>. Four groups of male SD rats were formed: control (0 mg/kg.bw), low (1 mg/kg.bw), medium (5 mg/kg.bw), and high-dose (25 mg/kg.bw) PM<sub>2.5</sub> groups. Experimental rats were subjected to PM<sub>2.5</sub> exposure via intratracheal instillation, given once weekly for 16 weeks. 24 h after the final exposure, blood, BALF, and lung tissues were collected. Pulmonary epithelial cells underwent cultivation and exposure to varying PM<sub>2.5</sub> concentrations with/without inhibitors for 24 h, after which total protein was extracted for relevant protein assays. The findings demonstrated that PM<sub>2.5</sub> damaged lung tissue to different degrees and led to PF in rats. Rats subjected to PM<sub>2.5</sub> exposure exhibited elevated concentrations of IL-9 protein in both serum and BALF, and elevated levels of IL-9 and its receptor, IL-9R, in lung tissues, compared to control counterparts. Furthermore, PM<sub>2.5</sub>-exposed groups demonstrated significantly augmented protein levels of p-STAT3, Snail, TWIST1, Vimentin, COL-I, and α-SMA, while displaying notably diminished levels of E-Cadherin compared to control group. The same findings were observed in PM<sub>2.5</sub>-treated cells. In BEAS-2B cells co-treated with Stattic (STAT3 inhibitor) and PM<sub>2.5</sub>, the opposite results occurred. Similar results were obtained for cells co-treated with IL-9-neutralizing antibody and PM<sub>2.5</sub>. Our findings suggest PM<sub>2.5</sub> mediates PF development by promoting IL-9 expression, leading to STAT3 phosphorylation and upregulation of Snail and TWIST1 expression, triggering EMT occurrence and progression in lung epithelial cells.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 12","pages":"4047 - 4058"},"PeriodicalIF":4.8000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Toxicology","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00204-024-03864-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

This study investigated the impact of PM2.5 on promoting EMT in PM2.5-induced pulmonary fibrosis (PF) development and explored molecular mechanisms of the IL-9/STAT3/Snail/TWIST1 signaling pathway in PF owing to PM2.5. Four groups of male SD rats were formed: control (0 mg/kg.bw), low (1 mg/kg.bw), medium (5 mg/kg.bw), and high-dose (25 mg/kg.bw) PM2.5 groups. Experimental rats were subjected to PM2.5 exposure via intratracheal instillation, given once weekly for 16 weeks. 24 h after the final exposure, blood, BALF, and lung tissues were collected. Pulmonary epithelial cells underwent cultivation and exposure to varying PM2.5 concentrations with/without inhibitors for 24 h, after which total protein was extracted for relevant protein assays. The findings demonstrated that PM2.5 damaged lung tissue to different degrees and led to PF in rats. Rats subjected to PM2.5 exposure exhibited elevated concentrations of IL-9 protein in both serum and BALF, and elevated levels of IL-9 and its receptor, IL-9R, in lung tissues, compared to control counterparts. Furthermore, PM2.5-exposed groups demonstrated significantly augmented protein levels of p-STAT3, Snail, TWIST1, Vimentin, COL-I, and α-SMA, while displaying notably diminished levels of E-Cadherin compared to control group. The same findings were observed in PM2.5-treated cells. In BEAS-2B cells co-treated with Stattic (STAT3 inhibitor) and PM2.5, the opposite results occurred. Similar results were obtained for cells co-treated with IL-9-neutralizing antibody and PM2.5. Our findings suggest PM2.5 mediates PF development by promoting IL-9 expression, leading to STAT3 phosphorylation and upregulation of Snail and TWIST1 expression, triggering EMT occurrence and progression in lung epithelial cells.

Abstract Image

Abstract Image

白细胞介素-9通过激活STAT3通路促进EMT介导的PM2.5诱导的肺纤维化
本研究探讨了PM2.5对促进PM2.5诱导的肺纤维化(PF)发展中EMT的影响,并探索了PM2.5导致的PF中IL-9/STAT3/Snail/TWIST1信号通路的分子机制。雄性SD大鼠分为四组:对照组(0 mg/kg.bw)、低剂量组(1 mg/kg.bw)、中剂量组(5 mg/kg.bw)和高剂量组(25 mg/kg.bw)。实验鼠通过气管内灌注接触 PM2.5,每周一次,持续 16 周。最终暴露 24 小时后,收集血液、BALF 和肺组织。培养肺上皮细胞并将其暴露于不同浓度的PM2.5(含/不含抑制剂)中24小时,然后提取总蛋白进行相关蛋白检测。研究结果表明,PM2.5 对大鼠的肺组织造成了不同程度的损伤,并导致了 PF。与对照组相比,暴露于PM2.5的大鼠血清和BALF中的IL-9蛋白浓度升高,肺组织中的IL-9及其受体IL-9R水平升高。此外,与对照组相比,PM2.5 暴露组的 p-STAT3、Snail、TWIST1、Vimentin、COL-I 和 α-SMA 蛋白水平明显升高,而 E-Cadherin 水平明显降低。在 PM2.5 处理的细胞中也观察到了同样的结果。在用 Stattic(STAT3 抑制剂)和 PM2.5 联合处理的 BEAS-2B 细胞中,出现了相反的结果。用 IL-9 中和抗体和 PM2.5 联合处理的细胞也得到了类似的结果。我们的研究结果表明,PM2.5通过促进IL-9的表达,导致STAT3磷酸化、Snail和TWIST1表达上调,引发肺上皮细胞EMT的发生和发展,从而介导PF的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信