SYVN1通过促进SIRT2泛素化降解在哮喘气道重塑中起保护作用
2024/01/26
摘要
背景：哮喘是一种以气道重塑为特征的异质性疾病。滑膜细胞凋亡抑制物1(SYVN1)作为E3连接酶，通过泛素化和降解介导内质网应激的抑制。然而，SYVN1在哮喘发病机制中的作用尚不清楚。
方法：在本研究中，我们利用卵清蛋白(OVA)诱导的小鼠模型来评估SYVN1对哮喘的影响。
结果：OVA诱导后小鼠肺组织中SYVN1表达增加。过表达SYVN1可减轻OVA诱导的气道炎症、杯状细胞增生和胶原沉积。体内实验中，SYVN1也抑制了内质网应激相关蛋白的增加和上皮-间充质转化(EMT)标志物的改变。利用TGF-β1体外诱导支气管上皮细胞(BEAS-2B)发生EMT。结果显示，TGF-β1刺激可下调SYVN1的表达，SYVN1过表达可阻止TGF-β1诱导的细胞内质网应激反应和EMT进程。此外，我们发现SYVN1与SIRT2结合并促进其泛素化和降解。SIRT2过表达可减弱SYVN1对内质网应激和EMT的保护作用。
结论：这些数据表明，SYVN1通过泛素化和降解SIRT2来抑制内质网应激，从而阻止EMT进程，从而保护哮喘气道重塑。
Role of SYVN1 in the control of airway remodeling in asthma protection by promoting SIRT2 ubiquitination and degradation
Bing Dai, Si Liu, Wenxin Shen, Li Chen, Qianlan Zhou, Lina Han, Qinzhen Zhang, Lishen Shan
Abstract
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.
METHODS:In the present study, an ovalbumin (OVA)-induced murine model was used to evaluate the effect of SYVN1 on asthma.
RESULTS: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.
背景：哮喘是一种以气道重塑为特征的异质性疾病。滑膜细胞凋亡抑制物1(SYVN1)作为E3连接酶，通过泛素化和降解介导内质网应激的抑制。然而，SYVN1在哮喘发病机制中的作用尚不清楚。
方法：在本研究中，我们利用卵清蛋白(OVA)诱导的小鼠模型来评估SYVN1对哮喘的影响。
结果：OVA诱导后小鼠肺组织中SYVN1表达增加。过表达SYVN1可减轻OVA诱导的气道炎症、杯状细胞增生和胶原沉积。体内实验中，SYVN1也抑制了内质网应激相关蛋白的增加和上皮-间充质转化(EMT)标志物的改变。利用TGF-β1体外诱导支气管上皮细胞(BEAS-2B)发生EMT。结果显示，TGF-β1刺激可下调SYVN1的表达，SYVN1过表达可阻止TGF-β1诱导的细胞内质网应激反应和EMT进程。此外，我们发现SYVN1与SIRT2结合并促进其泛素化和降解。SIRT2过表达可减弱SYVN1对内质网应激和EMT的保护作用。
结论：这些数据表明，SYVN1通过泛素化和降解SIRT2来抑制内质网应激，从而阻止EMT进程，从而保护哮喘气道重塑。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Biol Res. 2023 Dec 2;56(1):64 DOI: 10.1186/s40659-023-00478-7）
（Biol Res. 2023 Dec 2;56(1):64 DOI: 10.1186/s40659-023-00478-7）
Role of SYVN1 in the control of airway remodeling in asthma protection by promoting SIRT2 ubiquitination and degradation
Bing Dai, Si Liu, Wenxin Shen, Li Chen, Qianlan Zhou, Lina Han, Qinzhen Zhang, Lishen Shan
Abstract
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.
METHODS:In the present study, an ovalbumin (OVA)-induced murine model was used to evaluate the effect of SYVN1 on asthma.
RESULTS: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.
上一篇：
反式-IL-6 信号的上皮基因特征定义了 2 型低度哮喘亚群
下一篇：
17q21突变影响儿童哮喘黏膜宿主屏障
