Identification of novel target genes in human lung tissue involved in chronic obstructive pulmonary disease

鉴定与慢性阻塞性肺病有关的人类肺组织中的新靶基因

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作者:Lena Heinbockel, Sebastian Marwitz, Andra B Schromm, Henrik Watz, Christian Kugler, Ole Ammerpohl, Karoline Schnepf, Klaus F Rabe, Daniel Droemann, Torsten Goldmann

Discussion

MFGE8 turned out to be an interesting new candidate gene in COPD deserving further studies.

Methods

Tissues were subjected to transcriptome analysis. Candidate genes were identified and validated by immunohistochemistry. Primary human lung cells were subjected to stimulation with cigarette smoke extract for further validation by real time PCR.

Results

Six candidate genes were selected for further investigations: Aquaporin 3 (AQP3), extracellular matrix protein 1 (ECM1), four and a half LIM domain 1 (FHL1), milk fat globule epidermal growth factor 8 (MFGE8, lactadherin), phosphodiesterase 4D-interacting protein (PDE4DIP), and creatine transporter SLC6A8. All six proteins were allocated to distinct cell types by immunohistochemistry. Upon stimulation with cigarette smoke extract, human type II pneumocytes showed a dose-dependent down-regulation of MFGE8, while ECM1 and FHL1 also tended to be down-regulated. Although present, none of the candidates was regulated by cigarette smoke extract in primary human macrophages.

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