The mechanism of secreted frizzled-related protein 1 in alleviating cardiomyocyte injury and heart failure

Figures

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  Figure 1. Sfrp1 Molecular Structure Diagram. Diagram showing the relationship between CRD, a linker, and a Frizzled-like domain. CRD contains ten conserved cysteine residues and blocks the Wnt/β-catenin pathway. The linker provides a flexible connection for structural adaptation. The Frizzled-like domain mediates non- classical pathways such as Hippo and Notch.

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  Figure 2. Sfrp1 inhibits the classical Wnt/β-catenin signaling pathway. Diagram illustrating the classic Wnt/β-catenin signaling pathway. The WNT OFF state shows pathway deactivation with SFRP1 inhibiting Wnt, leading to active GSK-3β degrading β-catenin. The WNT ON state shows Wnt binding to the receptor, inactivating GSK-3β and accumulating β-catenin, which translocates to the nucleus and interacts with Tcf/Lef for gene transcription, promoting cell proliferation. The membrane, cytoplasm, and nucleus are labeled. Red circles indicate phosphorylated sites.

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  Figure 3. Sfrp1 inhibits the generation of oxygen free radicals. Diagram illustrating the classic Wnt/β-catenin signaling pathway. The WNT OFF state shows pathway deactivation with SFRP1 inhibiting Wnt, leading to active GSK-3β degrading β-catenin. The WNT ON state shows Wnt binding to the receptor, inactivating GSK-3β and accumulating β-catenin, which translocates to the nucleus and interacts with Tcf/Lef for gene transcription, promoting cell proliferation. The membrane, cytoplasm, and nucleus are labeled. Red circles indicate phosphorylated sites.

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  Figure 4. Sfrp1 inhibits cardiomyocyte proliferation through interactions with three signaling pathway. Diagram illustrating how SFRP1 interacts with and regulates signaling pathways including Notch, Wnt, and Hippo in cellular processes. It shows SFRP1's potential in blocking proliferation, highlighting actions like phosphorylation and β-catenin accumulation. The pathways influence cell adhesion, polarity, and gene transcription, impacting cardiac regeneration and myocardial cell proliferation.

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  Figure 5. Sfrp1 inhibits myocardial fibrosis by suppressing the binding of TGF-β1 to its receptor. Diagram illustrating the TGF-β signaling pathway. It shows the binding of TGF-β1 to TBR I and II receptors on the cell membrane, phosphorylation of Smad proteins, and their translocation into the nucleus. The activated complex influences transcription factors affecting apoptosis, cell proliferation, and tissue repair. Components like ATP, ADP, and SFRP1 are also depicted. Arrows indicate direct and indirect regulation effects.

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  Figure 6. Sfrp1 initiates the autophagy program by inhibiting the Wnt/β-catenin signaling pathway, clears apoptotic cardiomyocytes, and regulates the mitochondrial apoptotic pathway. Flowchart depicting the effects of SFRP1 upregulation in cardiac cells. Key pathways include inhibition of the Wnt/β-catenin signaling, leading to downregulation of Bax protein, decreased Cyt-c release, and reduced Caspase-9 activation, thus inhibiting apoptosis and reducing myocardial cell death. Increased autophagy-related gene expression promotes recovery of myocardial cells and delays cardiac function decline.

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  Figure 7. Sfrp1 synergistically regulates CREB phosphorylation and calcium metabolism. Diagram illustrating cellular signaling pathways involving calcium ions (Ca²+) and the role of SFRP1. It shows processes such as ATP synthesis, cell energy balance, and cellular responses. Key elements include a mitochondrial diagram highlighting MICU1, MCU, and the interactions affecting ATP output and calcium-induced cell death. Other paths detail electron transport chain activity and the involvement of SAC, cAMP, PKA, and CREB in gene regulation related to myocardial hypertrophy. The flow shows escalating reactions impacting cellular functions, modulated by SFRP1 and reactive oxygen species (ROS).