Targeting fibroblast invasion for pulmonary fibrosis

A method for identifying a therapeutic compound effective to reduce invasiveness of fibroblasts characterized by a highly invasive phenotype obtained from a subject with idiopathic pulmonary fibrosis, wherein such highly invasive phenotype is characterized by upregulation of one or more of genes selected from Krtap2-3, Involucrin, PODXL, IL7R, TAF12, MGA2, and BNC1 and downregulation of one or more genes selected from GPNMB, VAMP1, Patched1, NR4A2 and NEAT1, comprising

• a. Purifying a population of the fibroblasts characterized by the highly invasive phenotype by:
• i. Confirming expression of cell surface markers Krtap2-3high and Patched1negative by the invasive fibroblasts by flow cytometry;
• ii. isolating and establishing single cell clones based on expression of the cell surface markers;
• iii. Transfecting into IPF fibroblasts one or more mammalian expression pcDNA3-XFP vectors selected from the group of Krtap23-GFP, PODXL-RFP, CD127-CFP and PTCH1-mCherry comprising a promoter of Krtap23, PODXL, CD127, or Patched1 inserted upstream of the fluorescent protein tag;
• iv. Selecting positive cells of XFP expression;
• and
• v. Determining cell marker expression, matrix production, proliferation, survival, migration and invasive capacity of the transfected cells,
• b. Contacting the population of fibroblasts characterized by the highly invasive phenotype with a prospective therapeutic compound;
• and
• c. Reducing invasiveness of the fibroblasts as measured in an invasiveness assay, with minimal impact on normal lung fibroblasts with a non-invasive phenotype.