Multiple Roles of sFRP2 in Cardiac Development and Cardiovascular Disease

Figures

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  Figure 1. The canonical Wnt/β-catenin pathway. When the canonical Wnt/β-catenin pathway is “on”, the receptor complex consisting of frizzled and low-density lipoprotein receptor-related protein (LRP)5/6 bind WNT, which recruits the disheveled (DVL) protein to the plasma membrane. Subsequently, several components of the β-catenin destruction complex are recruited to the membrane, where they inhibit β-catenin ubiquitination and degradation, leading to stable accumulation of β-catenin in the cytoplasm. Lymphocyte enhancement factor/ T-cell factor (LEF/TCF) then binds to β-catenin to regulate the expression of target genes downstream of the Wnt pathway.

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  Figure 2. Interaction of sFRPs and Wnt signaling pathways. (A,B) sFRPs bind to Wnt through a cysteine-rich domain (CRD) or a C-terminal netrin-like domain (NTR), or bind to the frizzled receptor to form a non-functional complex that inhibits Wnt signaling. (C, D) sFRP interacts to form dimers, or promotes Wnt by transporting Wnt proteins to frizzled or by binding directly to frizzled during signal transduction. sFRP, secreted frizzle-related protein.

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  Figure 3. Role of sFRP2 in cardiovascular disease. (A) sFRP2 at low concentration activates the canonical Wnt/β-catenin pathway and enhances procollagen C protease activity in mammalian bone morphogenetic protein 1 (BMP1), eventually lead to cardiac fibrosis. (B) sFRP2 at high concentration inhibits the canonical Wnt/β-catenin pathway and attenuates procollagen C protease activity in mammalian BMP1, eventually leading to inhibition of cardiac fibrosis. (C) sFRP2 induces endothelial angiogenesis via the non-canonical Wnt/Ca2+/NFAT/Fzd5 pathway. (D) sFRP2 protects the heart from hypertrophy by inhibiting the canonical Wnt/β-catenin pathway. sFRP, secreted frizzle-related protein.