title: CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity.
  
  
  
  We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor.
  
  
  
  Lung tissue from IPF patients exhibited significantly greater expression of Hh-related genes versus controls. The gene most significantly upregulated in both IPF lung biopsies and fibroblasts stimulated in vitro with SHh wasCXCL14, which encodes a soluble secreted chemokine whose expression is inhibited in vitro by the addition of vismodegib.CXCL14expression was induced by SHh overexpression in mouse lung. Circulating CXCL14 protein levels were significantly higher in plasma from IPF patients than controls. In cancer patients, circulating CXCL14 levels were significantly reduced upon vismodegib treatment.
  
  
  
  CXCL14 is a systemic biomarker that could be used to identify IPF patients with increased Hh pathway activity and monitor the pharmacodynamic effects of Hh antagonist therapy in IPF.
  
  
  
  Post-results, NCT00968981.
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Guiquan
authors.initials: G
authors.lastname: Jia
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Chandriani
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Abbas
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Daryle J
authors.initials: DJ
authors.lastname: DePianto
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Elsa N
authors.initials: EN
authors.lastname: N'Diaye
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Murat B
authors.initials: MB
authors.lastname: Yaylaoglu
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Moore
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Peng
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: DeVoss
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Harold R
authors.initials: HR
authors.lastname: Collard
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wolters
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Jackson G
authors.initials: JG
authors.lastname: Egen
authors.affiliation: Genentech, Inc., South San Francisco, California, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Arron
mesh_terms: D000368:Aged; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D015415:Biomarkers; C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines
keywords: Idiopathic pulmonary fibrosis