title: Procollagen C-Proteinase Enhancer 1 (PCPE-1) as a Plasma Marker of Muscle and Liver Fibrosis in Mice.
abstract: Current non-invasive diagnostic methods of fibrosis are limited in their ability to identify early and intermediate stages of fibrosis and assess the efficacy of therapy. New biomarkers of fibrosis are therefore constantly sought for, leading us to evaluate procollagen C-proteinase enhancer 1 (PCPE-1), a fibrosis-related extracellular matrix glycoprotein, as a plasma marker of fibrosis. A sandwich ELISA that permitted accurate measurements of PCPE-1 concentrations in mouse plasma was established. Tissue fibrosis was assessed using histochemical, immunofluorescence, and immunoblotting analyses for type I collagen and PCPE-1. The normal plasma concentration of PCPE-1 in 6 weeks to 4 months old mice was ~200 ng/ml (189.5 ± 11.3 to 206.8 ± 13.8 ng/ml). PCPE-1 plasma concentrations in four and 8.5 months old mdx mice displaying fibrotic diaphragms increased 27 and 40% respectively relatively to age-matched control mice, an increase comparable to that of the N-propeptide of procollagen type III (PIIINP), a known blood marker of fibrosis. PCPE-1 plasma levels in mice with CCl4-induced liver fibrosis increased 34 to 50% relatively to respective controls and reflected the severity of the disease, namely increased gradually during the progression of fibrosis and went down to basal levels during recovery, in parallel to changes in the liver content of collagen I and PCPE-1. The results favor PCPE-1 as a potential new clinically valuable fibrosis biomarker.
authors.affiliation: Maurice and Gabriela Goldschleger Eye Research Institute, Tel-Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Tel-Hashomer, 52621, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Hassoun
authors.affiliation: Maurice and Gabriela Goldschleger Eye Research Institute, Tel-Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Tel-Hashomer, 52621, Israel.
authors.forename: Mary
authors.initials: M
authors.lastname: Safrin
authors.affiliation: Maurice and Gabriela Goldschleger Eye Research Institute, Tel-Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Tel-Hashomer, 52621, Israel.
authors.forename: Hana
authors.initials: H
authors.lastname: Ziv
authors.affiliation: Maurice and Gabriela Goldschleger Eye Research Institute, Tel-Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Tel-Hashomer, 52621, Israel.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pri-Chen
authors.affiliation: Maurice and Gabriela Goldschleger Eye Research Institute, Tel-Aviv University Sackler Faculty of Medicine, Sheba Medical Center, Tel-Hashomer, 52621, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Kessler