Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0231335 Publication Model: Print Cited Medium: Internet ISSN: 1931-3543 (Electronic) Linking ISSN: 00123692 NLM ISO Abbreviation: Chest Subsets: MEDLINE
    • Publication Information:
      Publication: 2016- : New York : Elsevier
      Original Publication: Chicago : American College of Chest Physicians
    • Subject Terms:
      Biomarkers/*metabolism ; Calcium-Binding Proteins/*metabolism ; Fibroblasts/*metabolism ; Idiopathic Pulmonary Fibrosis/*metabolism; Aged ; Aged, 80 and over ; Australia ; Blotting, Western ; Cell Culture Techniques ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Italy ; Male ; Middle Aged ; United States
    • Abstract:
      Background: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF.
      Methods: Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry.
      Results: Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = -0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012).
      Conclusions: Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments.
    • References:
      Exp Gerontol. 2007 Oct;42(10):1003-11. (PMID: 17706388)
      Mol Cell Endocrinol. 2012 Apr 4;351(2):167-75. (PMID: 22266540)
      PLoS One. 2010 Oct 13;5(10):e13360. (PMID: 20967215)
      Am J Respir Crit Care Med. 2012 Nov 1;186(9):814-6. (PMID: 23118079)
      J Cell Biol. 2010 Aug 23;190(4):693-706. (PMID: 20733059)
      J Clin Invest. 2011 Jun;121(6):2065-73. (PMID: 21633173)
      Am J Physiol Lung Cell Mol Physiol. 2008 Dec;295(6):L1007-17. (PMID: 18849439)
      J Proteome Res. 2011 Nov 4;10(11):4925-34. (PMID: 21888404)
      Histochem Cell Biol. 2009 Nov;132(5):559-65. (PMID: 19693531)
      Mol Cell Biol. 2001 Oct;21(20):7025-34. (PMID: 11564885)
      J Histochem Cytochem. 1995 Apr;43(4):401-11. (PMID: 7534784)
      Placenta. 2011 Feb;32(2):168-74. (PMID: 21145106)
      Transl Res. 2012 Apr;159(4):218-27. (PMID: 22424426)
      Thorax. 2013 Feb;68(2):155-62. (PMID: 23143842)
      Eur Respir J Suppl. 2001 Sep;32:2s-16s. (PMID: 11816822)
      Histochem J. 1996 Feb;28(2):109-16. (PMID: 8737292)
      Am J Respir Crit Care Med. 2012 Jan 1;185(1):67-76. (PMID: 22016448)
      Annu Rev Pathol. 2010;5:77-98. (PMID: 20078216)
      Ann Intern Med. 2013 May 7;158(9):641-9. (PMID: 23648946)
      BMJ. 1996 Sep 21;313(7059):744. (PMID: 8819450)
      Nat Rev Drug Discov. 2010 Feb;9(2):129-40. (PMID: 20094055)
      Am J Physiol Lung Cell Mol Physiol. 2012 Dec 15;303(12):L1046-56. (PMID: 23043074)
      Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824. (PMID: 21471066)
      Eur Respir J. 2013 Sep;42(3):750-7. (PMID: 23222877)
      Cell Tissue Res. 2012 Jan;347(1):103-16. (PMID: 21845400)
      Exp Biol Med (Maywood). 2008 Feb;233(2):109-22. (PMID: 18222966)
      Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1819-28. (PMID: 8970376)
      N Engl J Med. 2011 Apr 21;364(16):1503-12. (PMID: 21506741)
    • Grant Information:
      R01 HL095067 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Biomarkers)
      0 (Calcium-Binding Proteins)
      0 (fibulin)
    • Publication Date:
      Date Created: 20140517 Date Completed: 20141204 Latest Revision: 20240508
    • Publication Date:
      20240508
    • Accession Number:
      PMC4188142
    • Accession Number:
      10.1378/chest.13-2688
    • Accession Number:
      24832167