PT  - JOURNAL ARTICLE
AU  - Sebastian Marwitz
AU  - Gernot Zissel
AU  - Peter Zabel
AU  - Christian Kugler
AU  - Ekkehard Vollmer
AU  - Torsten Goldmann
TI  - <em>Ex vivo</em> trans-differentiation of primary human alveolar epithelial cells type II by TGFb
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P3509
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P3509.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P3509.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Lung fibrosis, especially idiopathic pulmonary fibrosis (IPF) as an end-stage lung disease, is characterized by irreversible collagen-deposition from myofibroblasts in the alveolar interstitium. Since IPF is regarded as resistant to anti-inflammatory therapy, the 5-years-survival rate is comparable to lung cancer and transplantation often remains the only curative treatment option. Up to date several theories exist about the origin of collagen-secreting myofibroblasts and the involvement of the transforming growth factor beta (TGFb) pathway.Here we present an ex vivo approach to investigate the role of human primary alveolar cells type II (AECII) as possible targets of the TGFb pathway with implications for IPF pathophysiology. Primary human AECII were isolated from tumor-free lungs and stimulated with TGFb and SB431542 to verify the pathway specificity. Actin cytoskeleton remodelling was assessed by phalloidin staining to investigate TGFb-dependent changes in cell morphology. Furthermore, changes in transdifferentiation marker expression were analyzed by immunocytochemistry or immunofluorescence. Gene expression analysis was conducted by means of qRT-PCR and microarrays. Our data show a significantly regulated TGFb pathway as well as expression of transdifferentiation markers upon stimulation in human AECII. Actin cytoskelett-remodelling was observed and an increased expression of collagen synthesis on both, RNA and protein level. Gene ontology (GO) enrichment revealed a significant number of developmental, differentiation and collagen synthesis terms in AECII by stimulation with TGFb.