Role of endoplasmic reticulum stress in impaired neonatal lung growth and bronchopulmonary dysplasia.
Role of endoplasmic reticulum stress in impaired neonatal lung growth and bronchopulmonary dysplasia.
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DOI：
10.1371/journal.pone.0269564
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
在高氧环境下饲养的幼鼠肺中，髓过氧化物酶（MPO）、氧化应激（OS）和内质网（ER）应激增加，这是支气管肺发育不良（BPD）的一种已建立的模型。然而，OS，MPO和ER应激之间的关系尚未在高氧大鼠幼崽中进行研究。我们用衣霉素或高氧处理Sprague-Dawley大鼠幼仔以确定这种关系。ER应激检测使用免疫荧光，转录组学，蛋白质组学，和电子显微镜分析。免疫荧光观察到高氧大鼠BPD和人BPD肺中ER应激增加。蛋白质组学和形态计量学研究表明，衣霉素直接增加大鼠肺的ER应激，降低肺的复杂性与BPD表型。以前，我们发现高氧启动了一个破坏循环，我们假设从增加OS通过MPO积累，然后增加ER应激引起BPD。为了抑制ER应激，我们使用了牛磺熊去氧胆酸（TUDCA），一种分子伴侣。为了打破破坏循环并减少OS和MPO，我们使用N-乙酰基-赖氨酰酪氨酰半胱氨酸酰胺（KYC）。TUDCA改善衣霉素和高氧处理的幼鼠肺复杂性的事实支持了ER应激在BPD中起因果作用的观点。其他支持来自数据显示，TUDCA降低了衣霉素和高氧处理的大鼠幼仔肺中的肺髓样细胞和MPO水平。这些数据将OS和MPO与ER应激在介导BPD的机制中联系起来。KYC对衣霉素处理的幼鼠肺中ER应激的抑制为MPO诱导的ER应激在BPD表型中起因果作用的观点提供了额外的支持。ER压力似乎扩大了我们提出的破坏周期。我们的研究结果表明，ER应激从OS和MPO演变为增加新生儿肺损伤和损害生长发育。TUDCA的令人鼓舞的效果表明该化合物具有治疗BPD的潜力。
Myeloperoxidase (MPO), oxidative stress (OS), and endoplasmic reticulum (ER) stress are increased in the lungs of rat pups raised in hyperoxia, an established model of bronchopulmonary dysplasia (BPD). However, the relationship between OS, MPO, and ER stress has not been examined in hyperoxia rat pups. We treated Sprague-Dawley rat pups with tunicamycin or hyperoxia to determine this relationship. ER stress was detected using immunofluorescence, transcriptomic, proteomic, and electron microscopic analyses. Immunofluorescence observed increased ER stress in the lungs of hyperoxic rat BPD and human BPD. Proteomic and morphometric studies showed that tunicamycin directly increased ER stress of rat lungs and decreased lung complexity with a BPD phenotype. Previously, we showed that hyperoxia initiates a cycle of destruction that we hypothesized starts from increasing OS through MPO accumulation and then increases ER stress to cause BPD. To inhibit ER stress, we used tauroursodeoxycholic acid (TUDCA), a molecular chaperone. To break the cycle of destruction and reduce OS and MPO, we used N-acetyl-lysyltyrosylcysteine amide (KYC). The fact that TUDCA improved lung complexity in tunicamycin- and hyperoxia-treated rat pups supports the idea that ER stress plays a causal role in BPD. Additional support comes from data showing TUDCA decreased lung myeloid cells and MPO levels in the lungs of tunicamycin- and hyperoxia-treated rat pups. These data link OS and MPO to ER stress in the mechanisms mediating BPD. KYC’s inhibition of ER stress in the tunicamycin-treated rat pup’s lung provides additional support for the idea that MPO-induced ER stress plays a causal role in the BPD phenotype. ER stress appears to expand our proposed cycle of destruction. Our results suggest ER stress evolves from OS and MPO to increase neonatal lung injury and impair growth and development. The encouraging effect of TUDCA indicates that this compound has the potential for treating BPD.
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影响因子：
5.8
作者：
Chen AC;Burr L;McGuckin MA
通讯作者：
McGuckin MA
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3.7
作者：
Henschel AM;Cabrera SM;Kaldunski ML;Jia S;Geoffrey R;Roethle MF;Lam V;Chen YG;Wang X;Salzman NH;Hessner MJ
通讯作者：
Hessner MJ
DOI：
10.1165/rcmb.2015-0327oc
发表时间：
2016-07-01
影响因子：
6.4
作者：
Flodby, Per;Li, Changgong;Zhou, Beiyun
通讯作者：
Zhou, Beiyun
影响因子：
5.1
作者：
Heubi, JE;Wiechmann, DA;Rhodes, P
通讯作者：
Rhodes, P