CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis
| Autor: | Joseph R. Arron, Ivan Peng, Jason DeVoss, Harold R. Collard, Alexander R. Abbas, Elsa N N'Diaye, Paul J. Wolters, Guiquan Jia, Murat Yaylaoglu, Jackson G. Egen, Daryle Depianto, Sanjay Chandriani, Heather M. Moore |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Male Pathology medicine.medical_specialty Pyridines Vismodegib Antineoplastic Agents 03 medical and health sciences Idiopathic pulmonary fibrosis Neoplasms medicine Animals Humans Anilides Hedgehog Proteins Sonic hedgehog CXCL14 Hedgehog Lung Cells Cultured Aged biology business.industry Cancer respiratory system Middle Aged medicine.disease Idiopathic Pulmonary Fibrosis respiratory tract diseases Up-Regulation Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation biology.protein Biomarker (medicine) Female business Chemokines CXC Biomarkers medicine.drug Signal Transduction |
| Zdroj: | Thorax. 72(9) |
| ISSN: | 1468-3296 |
| Popis: | Background 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. Methods 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. Results 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 was CXCL14 , which encodes a soluble secreted chemokine whose expression is inhibited in vitro by the addition of vismodegib. CXCL14 expression 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. Conclusions 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. Trial registration number Post-results, NCT00968981. |
| Databáze: | OpenAIRE |
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