Osteopontin contributes to late-onset asthma phenotypes in adult asthma patients.,Experimental & Molecular Medicine

当前位置： X-MOL 学术 › Exp. Mol. Med. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Osteopontin contributes to late-onset asthma phenotypes in adult asthma patients.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2020-02-03 , DOI: 10.1038/s12276-020-0376-2
Hoang Kim Tu Trinh _{1,

2} , Thuy Van Thao Nguyen ₃ , Seo-Hee Kim ₄ , Thi Bich Tra Cao ₄ , Quoc Quang Luu ₄ , Seung-Hyun Kim ₅ , Hae-Sim Park _{1,

4}

Affiliation

Patients with late-onset asthma (LOA) have poor clinical outcomes. Osteopontin (OPN) is associated with airway inflammation and remodeling. To investigate the role of OPN in LOA compared to early-onset asthma (EOA), serum OPN levels were compared between 131 adult asthma patients (48 LOA and 83 EOA patients) and 226 healthy controls (HCs). BALB/c mice were sensitized with ovalbumin with/without polyinosinic-polycytidylic acid (poly(I:C)) from week 6 (A6 mice) or week 12 (A12 mice) after birth. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF), cell counts, histology, and Spp1 expression were assessed. The levels of OPN, transforming growth factor β1 (TGF-β1), chitinase 3-like 1 (CH3L1), and interleukin (IL) 5 were measured by ELISA. The expression of Smad3 phosphorylation and tissue transglutaminase 2 (TGM2) was evaluated by Western blot. The serum OPN levels were significantly higher in asthma patients than in HCs and in LOA patients than in those with EOA (P < 0.05) and were positively correlated with serum TGF-β1 and CH3L1 (r = 0.174, r = 0.264; P < 0.05). A12 mice showed elevated AHR with increased levels of OPN/TGF-β1/IL-5 in BALF and Spp1 compared to A6 mice. Poly(I:C) induced remarkable TGF-β1, CH3L1, Th2 cytokine, and OPN levels in BALF and the expression of phosphorylated Smad3, TGM2, and Spp1 in the lungs. OPN triggered TGF-β1/Smad3 signaling in the lungs, which was suppressed by dexamethasone and anti-IL5 antibody. In conclusion, aging and exposure to viral infections may induce OPN release and consequently modulate inflammation and TGF-β1/Smad3-related remodeling, contributing to the development of LOA.

中文翻译：

骨桥蛋白有助于成年哮喘患者的迟发性哮喘表型。

迟发性哮喘（LOA）患者的临床预后较差。骨桥蛋白（OPN）与气道炎症和重塑有关。为了研究OPN在LOA与早期发作性哮喘（EOA）中的作用，比较了131名成年哮喘患者（48名LOA和83名EOA患者）和226名健康对照（HCs）的血清OPN水平。出生后第6周（A6小鼠）或第12周（A12小鼠）用卵清蛋白加/不加肌苷酸-聚胞苷酸（poly（I：C））使BALB / c小鼠致敏。评估气道高反应性（AHR），支气管肺泡灌洗液（BALF），细胞计数，组织学和Spp1表达。通过ELISA测量OPN，转化生长因子β1（TGF-β1），几丁质酶3样1（CH3L1）和白介素（IL）5的水平。通过蛋白质印迹评估Smad3磷酸化和组织转谷氨酰胺酶2（TGM2）的表达。哮喘患者的血清OPN水平显着高于HCs和LOA患者，高于EOA患者（P <0.05），并与血清TGF-β1和CH3L1正相关（r = 0.174，r = 0.264; P <0.05 ）。与A6小鼠相比，A12小鼠在BALF和Spp1中的AHR升高，OPN /TGF-β1/ IL-5水平升高。Poly（I：C）在BALF中诱导了显着的TGF-β1，CH3L1，Th2细胞因子和OPN水平以及肺中磷酸化Smad3，TGM2和Spp1的表达。OPN触发了肺中的TGF-β1/ Smad3信号传导，地塞米松和抗IL5抗体抑制了该信号。结论，

更新日期：2020-02-03

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文