Expression of cytochrome P450 mRNAs in Type II alveolar cells from subjects with chronic obstructive pulmonary disease.
Expression of cytochrome P450 mRNAs in Type II alveolar cells from subjects with chronic obstructive pulmonary disease.
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DOI：
10.1002/prp2.405
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发表时间：
2018-06
影响因子：
2.6
通讯作者：
Ichinose M
中科院分区：
文献类型：
--
作者：
Kamata S;Fujino N;Yamada M;Grime K;Suzuki S;Ota C;Tando Y;Okada Y;Sakurada A;Noda M;Matsuda Y;Sugiura H;Ichinose M
吸入药物对于慢性阻塞性肺疾病（COPD）等炎症性气道疾病的治疗至关重要。为了开发更好的肺部疾病治疗方法，了解肺部局部生物转化的分子机制具有潜在的重要性。肺泡上皮II型（ATII）细胞在肺内稳态中起关键作用，但对ATII细胞中编码细胞色素P450 （CYP）酶的基因表达模式知之甚少。此外，慢性阻塞性肺病中CYP基因表达的改变尚未完全确定。我们之前建立了一种利用荧光激活细胞分选从成人肺中纯化ATII细胞的方法。通过使用这种技术，我们在肺功能正常的非吸烟者（n = 4）和吸烟者（n = 4）的ATII细胞中测定了14种CYP酶的基因表达模式。尽管大多数CYP基因在原代肝细胞中高度表达，但我们发现，与肝细胞相比，ATII中CYP1B1 mRNA的表达量高出7.2倍（P = 0.0275）。此外，我们注意到与非COPD吸烟者（n = 4）相比，COPD患者（n = 3）分离的ATII细胞中CYP2C19上调3.0倍，CYP2J2 mRNA表达降低50%。这些数据首次详细介绍了人类ATII细胞中编码CYP酶的一整套基因，并强调了COPD患者CYP mrna的差异表达。这种认识可能对新型吸入药物的开发具有重要意义。
Inhaled drugs are critical for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD). To develop better therapeutics for pulmonary disease it is of potential importance to understand molecular mechanisms of local biotransformation in the lung. Alveolar epithelial type II (ATII) cells have a key role in homeostasis in the lung, but little is known about expression patterns of genes encoding cytochrome P450 (CYP) enzymes in ATII cells. In addition, alteration of CYP gene expression has not been fully defined in COPD. We previously established a method to purify ATII cells from the adult human lung using fluorescence‐activated cell sorting. By employing this technique we determined gene expression patterns of 14 CYP enzymes in ATII cells from nonsmokers (n = 4) and smokers (n = 4), both having normal pulmonary function. Although most CYP genes are highly expressed in primary hepatocytes, we found that CYP1B1 mRNA expression was 7.2‐fold higher in ATII compared to hepatocytes (P = .0275). Additionally we noted a 3.0‐fold upregulation of CYP2C19 and 50% reduction in CYP2J2 mRNA expressions in ATII cells isolated from patients with COPD (n = 3) compared to smokers without COPD (n = 4). These data, for the first time, detail a comprehensive set of genes encoding CYP enzymes in human ATII cells and highlights differentially expressed CYP mRNAs of patients with COPD. Such understanding may have important implications for the development of novel inhaled drugs.
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影响因子：
10.4
作者：
Thum, Thomas;Erpenbeck, Veit J;Moeller, Julia;Hohlfeld, Jens M;Krug, Norbert;Borlak, Jurgen
通讯作者：
Borlak, Jurgen
影响因子：
3.9
作者：
Bort, R;Gómez-Lechón, MJ;Jover, R
通讯作者：
Jover, R
DOI：
10.1152/ajpendo.00118.2014
发表时间：
2015-01-15
影响因子：
5.1
作者：
Li, Rui;Xu, Xizhen;Wang, Dao Wen
通讯作者：
Wang, Dao Wen
DOI：
10.1165/ajrcmb.16.3.9070608
发表时间：
1997-03-01
影响因子：
6.4
作者：
Anttila, S;Hukkanen, J;Raunio, H
通讯作者：
Raunio, H
影响因子：
--
作者：
Chen, Wenshu;Yang, Shijiang;Wang, Jianing
通讯作者：
Wang, Jianing