title: Towards a functional proteomics approach to the comprehension of idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis and pulmonary Langerhans cell histiocytosis.
abstract: Bronchoalveolar lavage fluid of patients with four interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, fibrosis associated to systemic sclerosis) and smoker and non smoker control subjects were compared in a proteomic study. Principal component analysis was used to statistically verify the association between differentially expressed proteins and the conditions analyzed. Pathway and functional analysis by MetaCore and DAVID software revealed possible regulatory factors involved in specific "process networks" like regulation of stress and inflammatory responses. Immune response by alternative complement pathways, protein folding, Slit-Robo signaling and blood coagulation were "pathway maps" possibly associated with interstitial lung diseases pathogenesis. Four interesting proteins plastin 2, annexin A3, 14-3-3ε and S10A6 (calcyclin) were validated by Western blot analysis. In conclusion, we identified proteins that could be directly or indirectly linked to the pathophysiology of the different interstitial lung diseases. Multivariate analysis allowed us to classify samples in groups corresponding to the different conditions analyzed and based on their differential protein expression profiles. Finally, functional and pathway analysis defined the potential function and relations among identified proteins, including low abundance molecules present in the MetaCore database.
  
  
  CONCLUSIONS
  This is the first study where different interstitial lung diseases such as sarcoidosis, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, fibrosis associated to systemic sclerosis and smoker and non smoker control subjects were compared in a proteomic study to highlight their common pathways. We decided to report not only principal component analysis, used to statistically verify the association between differentially expressed proteins and the conditions analyzed, but also functional analysis general results, considering all differential proteins potentially involved in these conditions, to speculate about possible common pathogenetic pathways involved in fibrotic lung damage.
authors.affiliation: Functional Proteomic Section, Department of Life Sciences, University of Siena, Siena, Italy. landi35@unisi.it
authors.forename: C
authors.initials: C
authors.lastname: Landi
authors.forename: E
authors.initials: E
authors.lastname: Bargagli
authors.forename: L
authors.initials: L
authors.lastname: Bianchi
authors.forename: A
authors.initials: A
authors.lastname: Gagliardi
authors.forename: A
authors.initials: A
authors.lastname: Carleo
authors.forename: D
authors.initials: D
authors.lastname: Bennett
authors.forename: M G
authors.initials: MG
authors.lastname: Perari
authors.forename: A
authors.initials: A
authors.lastname: Armini
authors.forename: A
authors.initials: A
authors.lastname: Prasse
authors.forename: P
authors.initials: P
authors.lastname: Rottoli
authors.forename: L
authors.initials: L
authors.lastname: Bini
mesh_terms: D000368:Aged; D030562:Databases, Protein; D005260:Female; D005786:Gene Expression Regulation; D006646:Histiocytosis, Langerhans-Cell / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics / Q000379:methods*; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012507:Sarcoidosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012907:Smoking / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012984:Software
chemical_list: D020543:Proteome