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

Introduction: As part of a study aimed at illuminating at least some of the complex molecular events taking place in COPD, we screened tissues by means of transcriptome analyses.

Materials and 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.

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