SYVN1通过促进SIRT2泛素化和降解在哮喘保护中控制气道重塑中的作用。

IF 4.3 2区 生物学 Q1 BIOLOGY
Bing Dai, Si Liu, Wenxin Shen, Li Chen, Qianlan Zhou, Lina Han, Qinzhen Zhang, Lishen Shan
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引用次数: 0

摘要

背景:哮喘是一种以气道重塑为特征的异质性疾病。SYVN1 (syno小提琴1)作为E3连接酶,通过泛素化和降解介导内质网(ER)应激的抑制。然而,SYVN1在哮喘发病机制中的作用尚不清楚。结果:本研究采用卵清蛋白(OVA)诱导的小鼠模型来评价SYVN1对哮喘的影响。小鼠卵诱导后肺中SYVN1表达增加。SYVN1过表达可减轻OVA诱导的气道炎症、杯状细胞增生和胶原沉积。在体内,SYVN1也抑制了内质网应激相关蛋白的增加和上皮-间质转化(EMT)标志物的改变。接下来,利用TGF-β1诱导的支气管上皮细胞(BEAS-2B)体外诱导EMT过程。结果表明,TGF-β1刺激可下调SYVN1的表达,SYVN1过表达可抑制TGF-β1诱导的细胞内质网应激反应和EMT过程。此外,我们发现SYVN1与SIRT2结合并促进其泛素化和降解。SIRT2过表达消除了SYVN1对体外ER应激和EMT的保护作用。结论:这些数据表明SYVN1通过泛素化和SIRT2降解来抑制内质网应激,从而阻断EMT过程,从而保护哮喘气道重塑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Role of SYVN1 in the control of airway remodeling in asthma protection by promoting SIRT2 ubiquitination and degradation.

Background: Asthma is a heterogenous disease that characterized by airway remodeling. SYVN1 (Synoviolin 1) acts as an E3 ligase to mediate the suppression of endoplasmic reticulum (ER) stress through ubiquitination and degradation. However, the role of SYVN1 in the pathogenesis of asthma is unclear.

Results: In the present study, an ovalbumin (OVA)-induced murine model was used to evaluate the effect of SYVN1 on asthma. An increase in SYVN1 expression was observed in the lungs of mice after OVA induction. Overexpression of SYVN1 attenuated airway inflammation, goblet cell hyperplasia and collagen deposition induced by OVA. The increased ER stress-related proteins and altered epithelial-mesenchymal transition (EMT) markers were also inhibited by SYVN1 in vivo. Next, TGF-β1-induced bronchial epithelial cells (BEAS-2B) were used to induce EMT process in vitro. Results showed that TGF-β1 stimulation downregulated the expression of SYVN1, and SYVN1 overexpression prevented ER stress response and EMT process in TGF-β1-induced cells. In addition, we identified that SYVN1 bound to SIRT2 and promoted its ubiquitination and degradation. SIRT2 overexpression abrogated the protection of SYVN1 on ER stress and EMT in vitro.

Conclusions: These data suggest that SYVN1 suppresses ER stress through the ubiquitination and degradation of SIRT2 to block EMT process, thereby protecting against airway remodeling in asthma.

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来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
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