Notch1/Hes1信号调控CCAAT/增强子结合蛋白α表达对高氧损伤肺泡Ⅱ型上皮细胞增殖与分化的影响 : = Effect of Notch1/Hes1 signal regulating the expression of CCAAT/enhancer-binding protein alpha on the proliferation and differentiation of type II alveolar epithelial cells induced by hyperoxia

背景:Notch1/Hes1信号和CCAAT/增强子结合蛋白α(CCAAT/enhancer-binding protein alpha,C/EBPα)在肺发育及肺损伤中均发挥重要作用。前期研究发现,高氧可引起肺泡Ⅱ型上皮细胞(typeⅡalveolar epithelialcell,AECII)增殖分化异常,并与C/EBPα异常表达有关,而这种异常是否与Notch1/Hes1信号调控有关,目前尚不清楚。目的:探讨Notch1/Hes1信号调控C/EBPα表达对高氧损伤AECII增殖与分化的影响。方法:体外培养人AECII,将细胞随机分为空气组、空气激活剂组(Notch通路激活剂Jagged1蛋白500μg/L)、高氧组(按3 L/min通入体积分数95%O_2和5%CO_2高纯混合气体且持续10 min)、高氧激活剂组(在通氧前30min加入Notch通路激活剂Jagged1蛋白500μg/L)。于干预后24h收获各组细胞,采用RT-PCR和Western blot法分别检测Notch1、Hes1及C/EBPαmRNA与蛋白表达水平;CCK-8法检测AECII细胞增殖;流式细胞术标记肺泡Ⅰ型上皮细胞特异性表面标志蛋白AQP5检测AECII分化。结果与结论:与空气组比,空气激活剂组Notch1、Hes1、C/EBPαmRNA和蛋白表达显著增加(P <0.05),AECII增殖增加而分化减少(P<0.05);高氧组和高氧激活剂组Notch1、Hes1、C/EBPαmRNA和蛋白表达显著降低(P <0.05),AECII增殖减少而分化增加(P <0.05);与高氧组比,高氧激活剂组Notch1、Hes1、C/EBPαmRNA和蛋白表达增加(P <0.05),AECII增殖增加而分化减少(P <0.05);结果提示,Notch1/Hes1信号可调控C/EBPα表达并能影响高氧损伤AECII增殖与分化功能。.

BACKGROUND: Notch1/Hes1 signal and CCAAT/enhancer-binding protein alpha(C/EBPα) play important roles in lung development and injury. Preliminary studies have shown that hyperoxia can induce abnormal proliferation and differentiation of type II alveolar epithelial cells(AECII),which is related to C/EBPα expression. But,whether Notch1/Hes1 signal is involved remains unclear. OBJECTIVE: To investigate the effect of Notch1/Hes1 signal regulating C/EBPα on the proliferation and differentiation of AECII induced by hyperoxia. METHODS: Human AECIIs were cultured in vitro,and randomly divided into air group,air activator group(Notch pathway activator Jagged1 protein,500 μg/L),hyperoxia group(95% O_2 and 5% CO_2 mixture gas administered at the speed of 3 L/minute for 10 minutes),hyperoxia activator group(500 μg/L Notch pathway activator Jagged1 protein added at 30 minutes before oxygen administration). AECIIs of each group were collected after 24 hours of intervention. The expression of Notch1,Hes1 and C/EBPα at mRNA and protein levels was determined by RT-PCR and western blot assay. The proliferation of AECII was measured by cell counting kit-8 assay. Flow cytometry labeled AQP5 was applied to detect the differentiation of AECII. RESULTS AND CONCLUSION: Compared with the air group,the mRNA and protein expression levels of Notch1,Hes1 and C/EBPα were increased significantly in the air activator group(P < 0.05),the proliferation of AECII was increased and the differentiation was reduced significantly(P < 0.05). In the hyperoxia and hyperoxia activator groups,the mRNA and protein expression levels of Notch1,Hes1 and C/EBPα were significantly decreased,the proliferation of AECII was decreased and the differentiation was increased significantly(P < 0.05). Compared with the hyperoxia group,the mRNA and protein expression levels of Notch1,Hes1 and C/EBPα were significantly increased in the hyperoxia activator group(P < 0.05),and the proliferation of AECII was increased and the differentiation was decreased significantly(P < 0.05). These results suggest that Notch1/Hes1 signal regulates the expression of C/EBPα and affects the proliferation and differentiation of AECII after exposure to hyperoxia..

Medienart:	E-Artikel

Erscheinungsjahr:	2018-08-23 17:03 2018
Erschienen:	2018-08-23 17:03

Enthalten in:	Zur Gesamtaufnahme - year:2018
Enthalten in:	Zhong guo zu zhi gong cheng yan jiu - (2018), 32 vom: 23 17:03. Aug., Seite 5209-5214 Original Letters: Enthalten in 中国组织工程研究 (DE-600)2994692-X (DE-600)2994692-X 辽宁省沈阳市

Reihe:	China Academic Journals (CAJ), E, 医药卫生科技 = Medicine & Public Health

Sprache:	Chinesisch

Weiterer Titel:	Effect of Notch1/Hes1 signal regulating the expression of CCAAT/enhancer-binding protein alpha on the proliferation and differentiation of type II alveolar epithelial cells induced by hyperoxia

Beteiligte Personen:	万峰云 [VerfasserIn] 卢红艳 [Sonstige Person] 万雪晴 [Sonstige Person] 郝晓波 [Sonstige Person] 朱玥 [Sonstige Person]

Links:	oversea.cnki.net [lizenzpflichtig]

Themen:	,Pulmonary Alveoli 上皮细胞:高氧症 内科学 分化 医药、卫生 医药卫生科技 呼吸系及胸部疾病 增殖 江苏大学附属医院儿科 组织工程 细胞分化 细胞增殖 肺泡 肺泡Ⅱ型上皮细胞 高氧 CCAAT增强子结合蛋白α CCAAT-Enhancer-Binding Protein-alpha Cell Differentiation Cell Proliferation Disease of Respiratory System Epithelial Cells Hyperoxia Medicine & Public Health Notch1/Hes1信号 Tissue Engineering

Anmerkungen:	Author info:Wan Feng-yun;Lu Hong-yan;Wan Xue-qing;Hao Xiao-bo;Zhu Yue;Department of Pediatrics,Affiliated Hospital of Jiangsu University

Förderinstitution / Projekttitel:

PPN (Katalog-ID):	CAJ605143854