ArticleJournal of molecular and cellular cardiology2009
Secreted frizzled related protein 2 protects cells from apoptosis by blocking the effect of canonical Wnt3a.
Article in Journal of molecular and cellular cardiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 120 citations in OpenAlex.
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- The scramblases VMP1 and TMEM41B are required for primitive endoderm specification by targeting WNT signaling.Cell death and differentiation · 2025Article
- EGFR and EGFRvIII coopt host defense pathways promoting progression in glioblastoma.Neuro-oncology · 2025Article
- Increased Secreted Frizzled-Related Protein 2 in Hypertension-Induced Left Ventricular Remodeling.Reviews in cardiovascular medicine · 2024Article
- Sfrp1 as a Pivotal Paracrine Factor in the Trained Pericardial Stem Cells that Foster Reparative Activity.Stem cells translational medicine · 2024Article
- Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation.International journal of molecular sciences · 2023Review
- Molecular Mechanism of Male Sterility Induced byMolecules (Basel, Switzerland) · 2023Article
- The secretome as a biomarker and functional agent in heart failure.The journal of cardiovascular aging · 2023Article
- Langerhans cells and SFRP2/Wnt/beta-catenin signalling control adaptation of skin epidermis to mechanical stretching.Journal of cellular and molecular medicine · 2022Article
- Wnt4 is crucial for cardiac repair by regulating mesenchymal-endothelial transition via the phospho-JNK/JNK.Theranostics · 2022Article
- Huoxin pill prevents acute myocardial ischaemia injury via inhibition of Wnt/β-catenin signaling.Journal of cellular and molecular medicine · 2021Article
- Yap Promotes Noncanonical Wnt Signals From Cardiomyocytes for Heart Regeneration.Circulation research · 2021Article
- LRP5 Regulates HIF-1α Stability via Interaction with PHD2 in Ischemic Myocardium.International journal of molecular sciences · 2021Article
- Article
- Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis.Cancer metastasis reviews · 2021Review
- Exercise in mice ameliorates high-fat diet-induced nonalcoholic fatty liver disease by lowering HMGCS2.Aging · 2021Article
- The role of Sfrp and DKK proteins in cardiomyocyte development.Physiological reports · 2021Review
- Lhx6 regulates canonical Wnt signaling to control the fate of mesenchymal progenitor cells during mouse molar root patterning.PLoS genetics · 2021Article
- Inverse Associations Between Circulating Secreted Frizzled Related Protein 2 (sFRP2) and Cardiometabolic Risk Factors.Frontiers in cardiovascular medicine · 2021Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
We have demonstrated that mesenchymal stem cells overexpressing the survival gene Akt can confer paracrine protection to ischemic myocytes both in vivo and in vitro through the release of secreted frizzled related protein 2 (Sfrp2). However, the mechanisms mediating these effects of Sfrp2 have not been fully elucidated. In this study, we studied rat cardiomyoblasts subjected to hypoxia reoxygenation (HR) injury to test the hypothesis that Sfrp2 exerts anti-apoptotic effect by antagonizing pro-apoptotic properties of specific Wnt ligands. We examined the effect of Wnt3a and Sfrp2 on HR-induced apoptosis. Wnt3a significantly increased cellular caspase activities and TUNEL staining in response to HR. Sfrp2 attenuated significantly Wnt3a-induced caspase activities in a concentration dependent fashion. Using a solid phase binding assay, our data demonstrates that Sfrp2 physically binds to Wnt3a. In addition, we observed that Sfrp2 dramatically inhibits the beta-catenin/TCF transcriptional activities induced by Wnt3a. Impressively, Dickkopf-1, a protein that binds to the Wnt coreceptor LRP, significantly inhibited the Wnt3a-activated caspase and transcriptional activities. Similarly, siRNA against beta-catenin markedly inhibited the Wnt3a-activated caspase activities. Consistent with this, significantly fewer TUNEL positive cells were observed in siRNA transfected cells than in control cells. Together, our data provide strong evidence to support the notion that Wnt3a is a canonical Wnt with pro-apoptotic action whose cellular activity is prevented by Sfrp2 through, at least in part, the direct binding of these molecules. These results can explain the in vivo protective effect of Sfrp2 and highlight its therapeutic potential for the ischemic heart.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.