title: MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?
abstract: BACKGROUND
  Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in hepatitis C patients. The current study aimed to evaluate serum levels of MFAP4 in patients with pulmonary fibrosis in order to test its potential as biomarker in clinical practice. A further aim was to determine whether MFAP4 deficiency in mice affects the formation of pulmonary fibrosis in the bleomycin model of lung fibrosis.
  
  
  METHODS
  91 patients with idiopathic pulmonary fibrosis (IPF), 23 with hypersensitivity pneumonitis (HP) and 31 healthy subjects were studied. In the mouse model, C57BL/6 Mfap4+/+ and Mfap4-/- mice between 6-8 weeks of age were studied. Serum levels of MFAP4 were measured by ELISA in patients and in mice. Surfactant protein D (SP-D) and LDH were measured as comparison biomarkers in patients with pulmonary fibrosis. Morphometric assessment and the Sircol kit were used to determine the amount of collagen in the lung tissue in the mouse model.
  
  
  RESULTS
  Serum levels of MFAP4 were not elevated in lung fibrosis - neither in the patients with IPF or HP nor in the animal model. Furthermore no significant correlations with pulmonary function tests of IPF patients could be found for MFAP4. MFAP4 levels were increased in BAL of bleomycin treated mice with pulmonary fibrosis.
  
  
  CONCLUSIONS
  MFAP4 is not elevated in sera of patients with pulmonary fibrosis or bleomycin treated mice with pulmonary fibrosis. This may be due to different pathogenic mechanisms of liver and lung fibrogenesis. MFAP4 seems to be useful as serum biomarker for hepatic but not for lung fibrosis.
authors.affiliation: Department of Gastroenterology and Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. christian.moelleken@rub.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Mölleken
authors.forename: Gereon
authors.initials: G
authors.lastname: Poschmann
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonella
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.forename: Kai
authors.initials: K
authors.lastname: Stühler
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Wolff H
authors.initials: WH
authors.lastname: Schmiegel
authors.forename: Niels
authors.initials: N
authors.lastname: Marcussen
authors.forename: Michael
authors.initials: M
authors.lastname: Helmer
authors.forename: Ole
authors.initials: O
authors.lastname: Nielsen
authors.forename: Søren
authors.initials: S
authors.lastname: Hansen
authors.forename: Anders
authors.initials: A
authors.lastname: Schlosser
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.forename: Grith Lykke
authors.initials: GL
authors.lastname: Sorensen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D016326:Extracellular Matrix Proteins / Q000097:blood* / Q000172:deficiency; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000172:deficiency; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000209:etiology; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C400752:MFAP4 protein, human; C000600072:MFAP4 protein, mouse
keywords: Biomarkers for pulmonary fibrosis, Idiopathic pulmonary fibrosis (IPF), Extracellular Matrix, Fibrogenesis, Mouse Model of Pulmonary Fibrosis