Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts.
Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts.
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DOI：
10.1038/pr.2015.27
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发表时间：
2015-05
影响因子：
3.6
通讯作者：
Uhal, Bruce D.
中科院分区：
文献类型：
--
作者：
Oarhe, Chinyere I.;Vinh Dang;MyTrang Dang;Hang Nguyen;Gopallawa, Indiwari;Gewolb, Ira H.;Uhal, Bruce D.
血管紧张素II（ANG）参与实验性高氧诱导的肺纤维化。血管紧张素转换酶-2（ACE-2）降解ANG II，因此具有保护作用，但在成人和实验性肺纤维化中下调。高氧是新生儿慢性纤维化肺病的已知原因，但ACE-2在新生儿肺纤维化中的作用尚不清楚。我们推测，ACE-2在人胎肺细胞可能下调高氧气体。将胎儿人肺成纤维细胞IMR 90细胞暴露于高氧（95%O2/5%CO2）或常氧（21%O2/5%CO2）气体中。分别回收细胞和培养基用于ACE-2酶活性、mRNA和免疫反应性蛋白的测定。高氧使IMR 90细胞ACE-2免疫反应蛋白和酶活性降低（均P < 0.01），但对ACE-2 mRNA表达无明显影响。ACE-2蛋白在细胞上清液中增加，表明蛋白酶介导的胞外域脱落。TAPI-2是一种TNF-α-转化酶（TACE/ADAM 17）抑制剂，可阻止细胞ACE-2的减少和可溶性ACE-2的增加（均P < 0.05）。这些数据表明，ACE-2在胎儿人肺成纤维细胞中表达，但被高氧气体显著降低。他们还表明，高氧通过ADAM 17/TACE介导的脱落机制降低ACE-2。本文的在线版本（doi：10.1038/pr.2015.27）包含补充材料，可供授权用户使用。
Angiotensin (ANG) II is involved in experimental hyperoxia-induced lung fibrosis. Angiotensin-converting enzyme-2 (ACE-2) degrades ANG II and is thus protective, but is downregulated in adult human and experimental lung fibrosis. Hyperoxia is a known cause of chronic fibrotic lung disease in neonates, but the role of ACE-2 in neonatal lung fibrosis is unknown. We hypothesized that ACE-2 in human fetal lung cells might be downregulated by hyperoxic gas. Fetal human lung fibroblast IMR90 cells were exposed to hyperoxic (95% O2/5% CO2) or normoxic (21% O2/5% CO2) gas in vitro. Cells and culture media were recovered separately for assays of ACE-2 enzymatic activity, mRNA, and immunoreactive protein. Hyperoxia decreased ACE-2 immunoreactive protein and enzyme activity in IMR90 cells (both P < 0.01), but did not change ACE-2 mRNA. ACE-2 protein was increased in the cell supernatant, suggesting protease-mediated ectodomain shedding. TAPI-2, an inhibitor of TNF-α−converting enzyme (TACE/ADAM17), prevented both the decrease in cellular ACE-2 and the increase in soluble ACE-2 (both P < 0.05). These data show that ACE-2 is expressed in fetal human lung fibroblasts but is significantly decreased by hyperoxic gas. They also suggest that hyperoxia decreases ACE-2 through a shedding mechanism mediated by ADAM17/TACE. The online version of this article (doi:10.1038/pr.2015.27) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
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DOI：
10.1152/ajplung.00313.2002
发表时间：
2004-01-01
影响因子：
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作者：
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影响因子：
16.6
作者：
Zou Z;Yan Y;Shu Y;Gao R;Sun Y;Li X;Ju X;Liang Z;Liu Q;Zhao Y;Guo F;Bai T;Han Z;Zhu J;Zhou H;Huang F;Li C;Lu H;Li N;Li D;Jin N;Penninger JM;Jiang C
通讯作者：
Jiang C
影响因子：
4
作者：
Agarwal B;Stowe DF;Dash RK;Bosnjak ZJ;Camara AK
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DOI：
10.1152/ajplung.00222.2010
发表时间：
2011-09-01
影响因子：
4.9
作者：
Uhal, Bruce D.;Li, Xiaopeng;Abdul-Hafez, Amal
通讯作者：
Abdul-Hafez, Amal