Decreased expression of autophagic beclin 1 protein in idiopathic pulmonary fibrosis fibroblasts

• Published in: Journal of cellular physiology 2013-07, Vol.228 (7), p.1516-1524
• Main Authors: Ricci, Alberto, Cherubini, Emanuela, Scozzi, Davide, Pietrangeli, Vittorio, Tabbì, Luca, Raffa, Salvatore, Leone, Laura, Visco, Vincenzo, Torrisi, Maria Rosaria, Bruno, Pierdonato, Mancini, Rita, Ciliberto, Gennaro, Terzano, Claudio, Mariotta, Salvatore
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - physiology; Apoptosis Regulatory Proteins - metabolism; Autophagy - drug effects; Autophagy - physiology; Beclin-1; Case-Control Studies; Cell Line; Cells, Cultured; Cisplatin - pharmacology; Female; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Humans; Idiopathic Pulmonary Fibrosis - metabolism; Idiopathic Pulmonary Fibrosis - pathology; Male; Membrane Proteins - metabolism; Molecular biology; Proto-Oncogene Proteins c-bcl-2 - metabolism
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.24307

Autophagy is the main cellular pathway for degradation of long‐lived proteins and organelles and regulates cell fate in response to stress. Beclin 1 is a key regulator of this process. In some settings autophagy and apoptosis seem to be interconnected. Recent reports indicate that fibroblasts in idiopathic pulmonary fibrosis (IPF) acquire resistance to apoptosis. Here, we examined the expression of beclin 1, and of the anti apoptotic protein Bcl‐2 in human IPF fibroblasts using immunohistochemistry and molecular biology in bioptic sections, in primary cultures of fibroblasts taken from patients with IPF and in fibroblast cell lines. Expression of beclin 1 in fibroblasts from IPF was down‐regulated in comparison with fibroblasts from normal lungs while the anti‐apoptotic protein Bcl‐2 expression was over‐expressed. Treatment of fibroblast cell cultures with cisplatin induced a significant increase in beclin 1 and caspase 3 protein levels but a reduction in Bcl‐2 expression. These observations were confirmed by the analysis of acid compartments and transmission electron microscopy. Our results demonstrate a modified expression of the apoptotic beclin 1 Bcl‐2 proteins in human IPF fibroblasts suggesting the existence of an autophagy/apoptosis system dysfunction. J. Cell. Physiol. 228: 1516–1524, 2013. © 2012 Wiley Periodicals, Inc.