Proteomic studies on receptor for advanced glycation end product variants in idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.
OBJECTIVE
Proteomic screening revealed declined levels of the receptor for advanced glycation end products (RAGE) in human idiopathic pulmonary fibrosis (IPF). This study was undertaken to investigate the different RAGE isoforms in two lung diseases with destruction of the lung parenchyma, i.e. IPF and chronic obstructive pulmonary disease (COPD).


METHODS
RAGE was analyzed by 2-DE, MS and Western blotting using lung tissues from non-smokers, smokers, patients with IPF, COPD and α-1-antitrypsin deficiency (AAT) and by ELISA from the bronchoalveolar lavage fluid samples.


RESULTS
RAGE, detected by 2-DE in the control lung, was confirmed to be glycosylated, soluble, C-truncated RAGE with characteristics indicative of the presence of endogenous secretory RAGE (esRAGE). Further studies revealed a decrease of the full length-RAGE (FL-RAGE) and its C-terminal processed variant (cRAGE) in the lung tissues of IPF and COPD patients but not in AAT. The esRAGE level was reduced in IPF but was unchanged in COPD.


CONCLUSIONS
This study shows an involvement of the three RAGE variants (FL-RAGE, cRAGE, esRAGE) in IPF. The decline of FL-RAGE and cRAGE, but not esRAGE, in COPD lungs is evidence of involvement of specific RAGE variants also in this disease.
Biocenter Oulu, Department of Biochemistry, University of Oulu, Finland.
Steffen
S
Ohlmeier
Witold
W
Mazur
Kaisa
K
Salmenkivi
Marjukka
M
Myllärniemi
Ulrich
U
Bergmann
Vuokko L
VL
Kinnula
D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism; D017384:Sequence Deletion; D012907:Smoking / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D008565:Membrane Proteins; D020033:Protein Isoforms; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human