MMP1 and MMP7 as potential peripheral blood biomarkers in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease associated with significant morbidity and mortality. We identified a combinatorial signature of 5 proteins that was sufficient to distinguish IPF patients from controls; of these proteins MMP7 and MMP1 exhibited significantly higher values in both peripheral blood concentrations and lung tissue gene expression, suggesting their role as true biomarkers. Keywords: disease versus control Lung tissue samples for microarray analysis were obtained through the University of Pittsburgh Health Sciences Tissue Bank. Twenty-three samples were obtained from surgical remnants of biopsies or lungs explanted from patients with IPF who underwent pulmonary transplant, eight patients with idiopathic pulmonary fibrosis whose pathological findings were indicative of the acute exacerbations, and 15 control normal lung tissues obtained from the disease free margins with normal histology of lung cancer resection specimens. The morphologic diagnosis of IPF was based on typical microscopic findings consistent with usual interstitial pneumonia. Total RNA was used as a template for synthesis of cDNA as recommended by the manufacturer of the arrays (Agilent Technologies, Santa Clara, CA). The cDNA was used as a template to generate Cy3 labeled cRNA that was used for hybridization on Agilent Whole Human Genome 4 X 44K multi pack arrays (Agilent Technologies, Santa Clara, CA). After 17 hours hybridization, arrays were washed and scanned according to the manufacturer’s protocol.