Synergistic effect of PCPE1 and sFRP2 on the processing of procollagens via BMP1
Synergistic effect of PCPE1 and sFRP2 on the processing of procollagens via BMP1
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DOI：
10.1002/1873-3468.13291
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发表时间：
2018-11
期刊：
影响因子：
3.5
通讯作者：
Qin Zhu;W. Guo;Shengjie Zhang;Yang Feng;Xiao Wang;Libin Zhou;Guo-Ru Huang
中科院分区：
文献类型：
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作者：
Qin Zhu;W. Guo;Shengjie Zhang;Yang Feng;Xiao Wang;Libin Zhou;Guo-Ru Huang
前胶原蛋白加工对于器官发育和组织功能至关重要。前胶原C蛋白酶增强子1（PCPE 1）和分泌型卷曲相关蛋白2（sFRP 2）通过调节骨形态发生蛋白1（BMP 1）的前胶原C蛋白酶活性在胶原形成中发挥重要作用。然而，这两种蛋白质是否对BMP 1活性产生协同作用仍不清楚。在这里，sFRP 2和PCPE 1的同时敲低导致小鼠胚胎成纤维细胞中胶原蛋白形成减少，斑马鱼胚胎中背侧化表型减少。进一步的研究揭示了sFRP 2的卷曲结构域与PCPE 1的补体/Uegf/BMP-1结构域之间的直接相互作用，这增强了BMP 1对前胶原的切割活性。这些结果表明，sFRP 2和PCPE 1的双重沉默可能提供治疗胶原沉积引起的纤维化疾病的策略。
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.