Gene expression analysis of membrane transporters and drug‐metabolizing enzymes in the lung of healthy and <scp>COPD</scp> subjects

Berg, Tove; Myrbäck, Tove Hegelund; Olsson, Marita; Seidegård, Janeric; Werkström, Viktoría; Zhou, Xin; Grünewald, Johan; Gustavsson, Lena; Nord, Magnus

doi:10.1002/prp2.54

Cited by 27 publications

(34 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These 2 enzymes are major CYP isoforms in human liver . The data presented here agrees previous studies showing no or very low expressions of CYP1A2 and CYP3A4 mRNAs in human lung tissue …”

Section: Resultssupporting

confidence: 92%

“…In contrast, CYP2J2 mRNA in COPD subjects was half the level of that in smokers (Figure ). These differences were not identified when whole‐lung tissues from smokers and COPD patients were used for analysis …”

Section: Resultsmentioning

confidence: 99%

“…The human pulmonary tissue also expresses a wide range of CYP enzymes to metabolize a great variety of inhaled xenobiotics and toxicants, but the expression pattern of lung CYPs substantially differ from metabolisms in the liver . A recent study using a comprehensive expression analysis for genes encoding membrane transporters and phase I and II drug‐metabolizing enzymes indicated that these gene expressions were not significantly altered in lung tissues from patients with COPD compared to healthy subjects . However, given previous reports indicating different expression patterns of drug‐metabolizing enzymes in cell populations such as alveolar epithelial cells, pulmonary vascular endothelial cells, and airway macrophages, cell‐type‐specific analyses are required to precisely define differences in CYP gene expression in lung tissues between healthy subjects and patients with pulmonary diseases.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7] A recent study using a comprehensive expression analysis for genes encoding membrane transporters and phase I and II drug-metabolizing enzymes indicated that these gene expressions were not significantly altered in lung tissues from patients with COPD compared to healthy subjects. 8 However, given previous reports indicating different expression patterns of drug-metabolizing enzymes in cell populations such as alveolar epithelial cells, pulmonary vascular endothelial cells, and airway macrophages, 9,10 cell-type-specific analyses are required to precisely define differences in CYP gene expression in lung tissues between healthy subjects and patients with pulmonary diseases. In the alveolar region alveolar epithelial type I (ATI) and type II (ATII) cells, together with alveolar macrophages constitute the major cellular population.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Expression of cytochrome P450 mRNAs in Type II alveolar cells from subjects with chronic obstructive pulmonary disease

Kamata

Fujino

Yamada

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

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.

show abstract

“…These 2 enzymes are major CYP isoforms in human liver . The data presented here agrees previous studies showing no or very low expressions of CYP1A2 and CYP3A4 mRNAs in human lung tissue …”

Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of cytochrome P450 mRNAs in Type II alveolar cells from subjects with chronic obstructive pulmonary disease

Kamata

Fujino

Yamada

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

show abstract

“…When we assessed the tumor-specific allelic expression, we identified 815 T-VSE and 830 T-VSL variants (Supplementary Tables S7 and S8). Among the redundant across samples observations are the T-VSE rs156697 in GSTO2 and the T-VSL rs144610753 in PER3 (33,34). …”

Section: Resultsmentioning

confidence: 99%

RNA2DNAlign: nucleotide resolution allele asymmetries through quantitative assessment of RNA and DNA paired sequencing data

et al. 2016

View full text Add to dashboard Cite

We introduce RNA2DNAlign, a computational framework for quantitative assessment of allele counts across paired RNA and DNA sequencing datasets. RNA2DNAlign is based on quantitation of the relative abundance of variant and reference read counts, followed by binomial tests for genotype and allelic status at SNV positions between compatible sequences. RNA2DNAlign detects positions with differential allele distribution, suggesting asymmetries due to regulatory/structural events. Based on the type of asymmetry, RNA2DNAlign outlines positions likely to be implicated in RNA editing, allele-specific expression or loss, somatic mutagenesis or loss-of-heterozygosity (the first three also in a tumor-specific setting). We applied RNA2DNAlign on 360 matching normal and tumor exomes and transcriptomes from 90 breast cancer patients from TCGA. Under high-confidence settings, RNA2DNAlign identified 2038 distinct SNV sites associated with one of the aforementioned asymetries, the majority of which have not been linked to functionality before. The performance assessment shows very high specificity and sensitivity, due to the corroboration of signals across multiple matching datasets. RNA2DNAlign is freely available from http://github.com/HorvathLab/NGS as a self-contained binary package for 64-bit Linux systems.

show abstract

Expression of xenobiotic metabolising enzymes in lungs of horses with or without histological evidence of lower airway inflammation

Löfgren

Larsson

Lindberg

et al. 2020

Veterinary Medicine & Sci

View full text Add to dashboard Cite

Mild, moderate and severe equine asthma is a problem for equine welfare. The aetiology of the disease is not known in detail but is likely multi‐factorial. One important factor may be inhaled dust which carries harmful substances which may be bioactivated and thus can lead to local inflammation in the airways. The aim of this study was to investigate gene expression and protein localisation of cytochrome P450 (CYP) enzymes, superoxide dismutase and glutathione‐S‐transferases (GST) involved in bioactivation and detoxification of harmful substances in lungs of horses with or without histological evidence of lower airway inflammation. Significantly lower gene expression of CYP2A13 and GSTM1 was observed in lungs from horses with histological evidence of lower airway inflammation compared with horses without. A higher expression, although not significant, was found for CYP1A1 in horses with histological evidence of lower airway inflammation. There were no differences in gene expression of GSTP1 and SOD3. The proteins were localised in the respiratory epithelium which is of relevance as a defence to local exposure of inhaled harmful substances. In conclusion, our study reports differential gene expression of enzymes involved in bioactivation and detoxification of foreign substances in the lungs of horses with histological evidence of lower airway inflammation compared with horses without.

show abstract

Gene expression analysis of membrane transporters and drug‐metabolizing enzymes in the lung of healthy and COPD subjects

Cited by 27 publications

References 32 publications

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

RNA2DNAlign: nucleotide resolution allele asymmetries through quantitative assessment of RNA and DNA paired sequencing data

Expression of xenobiotic metabolising enzymes in lungs of horses with or without histological evidence of lower airway inflammation

Contact Info

Product

Resources

About