Synergistic effect of PCPE1 and sFRP2 on the processing of procollagens via BMP1
FEBS LETTERS
Authors: Zhu, Qin; Guo, Wei; Zhang, Shengjie; Feng, Yang; Wang, Xiao; Zhou, Libin; Huang, Guo-Ru
Abstract
Procollagen processing is essential for organ development and tissue functions. Both procollagen C-proteinase enhancer 1 (PCPE1) and secreted frizzled-related protein 2 (sFRP2) play vital roles in collagen formation via regulating the procollagen C-proteinase activity of bone morphogenetic protein 1 (BMP1). However, whether the two proteins exert a synergistic effect on BMP1 activity remains unclear. Here, simultaneous knockdown of sFRP2 and PCPE1 led to less collagen formation in mouse embryonic fibroblasts and dorsalized phenotypes in zebrafish embryos. Further studies revealed a direct interaction between the Frizzled domain of sFRP2 and the complement/Uegf/BMP-1 domain of PCPE1, which enhances the cleavage activity of BMP1 on procollagen. These results suggest that double silencing of sFRP2 and PCPE1 may provide a strategy for treating fibrosis diseases caused by collagen deposition.
The Value of Signal Peptide-CUB-EGF Domain-containing Protein-1 (SCUBE1) in the Diagnosis of Pulmonary Embolism: A Preliminary Study
ACADEMIC EMERGENCY MEDICINE
Authors: Turkmen, Suha; Sahin, Aynur; Gunaydin, Mucahit; Sahin, Sinan; Mentese, Ahmet; Turedi, Suleyman; Karahan, Suleyman Caner; Ozsu, Savas; Gunduz, Abdulkadir
Abstract
ObjectivesThe diagnosis of pulmonary embolism (PE) in the emergency department still poses difficulties because symptoms and signs are nonspecific. There is a need for more reliable noninvasive diagnostic tests to support clinical suspicion before the costly invasive procedures with complication risks still used in the diagnosis of PE. Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF (epidermal growth factor) domain-containing protein 1 (SCUBE1) is a novel, secreted cell surface protein expressed during early embryogenesis. The goal of this study was to compare the SCUBE1 levels between PE patients and healthy subjects and also investigate the value of SCUBE1 in the diagnosis of PE. MethodsEleven patients diagnosed with PE using spiral computerized tomographic pulmonary angiography were included in the study. A control group of 23 age-matched, healthy volunteers served as a reference for biochemical parameters. ResultsMean (SD) SCUBE1 levels were 72.0 (+/- 32.6) ng/mL in the patients with PE and 31.4 (+/- 13.8) ng/mL in the control group. SCUBE1 levels were significantly higher in the patients with PE (p=0.001). Receiver operating characteristic (ROC) curve analysis was performed to determine cutoff thresholds in discriminating between PE and control group plasma SCUBE1 levels. Area under the ROC for that purpose was 0.862 (95% confidence interval [CI]=0.70 to 1). A SCUBE1 cutoff point in patients with PE>46ng/mL had specificity and sensitivity of 91% (95% CI=0.70% to 0.98%) and 82% (95% CI=0.48% to 0.97%), respectively. ConclusionsThis preliminary study suggests that plasma SCUBE1 values have a good level of specificity for PE and may be of use in the diagnosis of PE. Further studies involving larger case series and also clinical studies are needed to corroborate these findings. (C) 2015 by the Society for Academic Emergency Medicine (C) 2015 by the Society for Academic Emergency Medicine