PO101 - Myoferlin — new player in idiopathic pulmonary fibrosis pathogenesis?
Mimosa Peltokangas (Finland)1 2; Mervi Kreus (Finland)1 3; Steffen Ohlmeier (Finland)4; Siri Lehtonen (Finland)5; Henna karvonen (Finland)6; Elisa Lappi-Blanco (Portugal)7 8; Johanna Leppänen (Finland)1 2; Riitta Kaarteenaho (Finland)1 2;
1 - Research Unit of Biomedicine and Internal Medicine, University of Oulu, Oulu, Finland; 2 - Center of Internal Medicine and Respiratory Medicine, and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland; 3 - Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; 4 - Proteomics and Mass Spectrometry Core Facilities, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; 5 - Department of Obstetrics and Gynecology and Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland; 6 - Optomed, Oulu, Finland; 7 - Department of Pathology, Oulu University Hospital, Oulu, Finland; 8 - Department of Pathology, Research Unit of Translational Medicine, University of Oulu, Oulu, Finland;
Keywords: Myoferlin; Proteomics; Fibroblast;
Select the theme: Idiopathic Pulmonary Fibrosis
Type: Original Papers
Presentation: Poster Presentation

Introduction: Myoferlin is a conserved protein involved in membrane repair and endocytosis. It is upregulated across several types of cancer, including non-small cell lung cancer, in which it associates with poor prognosis. In idiopathic pulmonary fibrosis (IPF) tissues, myoferlin protein levels are upregulated in the honeycombs.

Objectives: We aimed to compare the proteomic profiles of stromal cell lines derived from IPF and lung cancers.

Materials and Methods: We studied proteomic profiles of stromal cell lines derived from 7 IPF, 12 adenocarcinoma (AC), and 6 squamous cell carcinoma (SQC) patients as well as controls (5 non-smokers and 7 smokers). Myoferlin expression in stromal cell lines (7 IPF, 4 AC, 4 SQC, and 8 controls) and lung tissue samples (8 IPF, 8 AC, 2 SQC, and 8 controls) were also studied by Western analysis and immunohistochemistry, respectively.

Results: Proteomics revealed 92 proteins or protein fragments that showed significantly altered abundance (p < 0.05) in at least one condition compared to the others. Notably, myoferlin protein levels in IPF were higher than in all other subgroups, with a significant increase relative to smoker controls (p=0.014) and SQC (p=0.018). Western blot analysis confirmed the same trend with significant increases in protein expressions (SQC vs. IPF p=0,004, Control vs. IPF p=0,028). In immunohistochemistry, 7/8 AC and 1/2 SQC tumor cells were myoferlin-positive, while stromal cells in all cases showed myoferlin positivity. In IPF, immunohistochemical expression of myoferlin was high in hyperplastic alveolar epithelium, and some stromal cells in fibroblast foci (5/8) were myoferlin-positive.

Conclusions: In conclusion, myoferlin protein levels were upregulated in IPF-derived stromal cell lines, and immunohistochemistry revealed strong myoferlin positivity in hyperplastic alveolar epithelium and stromal cells in IPF lung tissue samples. Thus, this study shows that myoferlin, earlier shown to be associated mainly with cancer pathogenesis, may also play a role in IPF.