ArticleProceedings of the National Academy of Sciences of the United States of America2015
Central role of SIAH inhibition in DCC-dependent cardioprotection provoked by netrin-1/NO.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Target degradation of CASPASE-1 for alleviation of inflammation in sepsisActa pharmaceutica Sinica. B · 2026Article
- N-palmitoyl glycine differentially modulates TRPM4 and TRPC5 and is causally linked to Brugada syndrome.Communications biology · 2025Article
- Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit.Nature communications · 2025Article
- Integrated bioinformatics analysis reveals Netrin-1 as a key molecular link between Parkinson's disease and heart failure.Frontiers in aging neuroscience · 2025Article
- Reversal of Pulmonary Hypertension in a Human-Like Model: Therapeutic Targeting of Endothelial DHFR.Circulation research · 2024Article
- Myeloid hypoxia-inducible factor HIF1A provides cardio-protection during ischemia and reperfusionFrontiers in cardiovascular medicine · 2022Article
- Alternative adenosine Receptor activation: The netrin-Adora2b link.Frontiers in pharmacology · 2022Review
- PMN-derived netrin-1 attenuates cardiac ischemia-reperfusion injury via myeloid ADORA2B signaling.The Journal of experimental medicine · 2021Article
- Neuronal guidance proteins in cardiovascular inflammation.Basic research in cardiology · 2021Review
- Characterization and functional analysis of SIAH1 during skin and hair follicle development in the angora rabbit (Oryctolagus cuniculus).Hereditas · 2020Article
- NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets.Nature reviews. Cardiology · 2020Review
- PHF19 promotes the proliferation, migration, and chemosensitivity of glioblastoma to doxorubicin through modulation of the SIAH1/β-catenin axis.Cell death & disease · 2018Article
- Dissecting the Role of the Extracellular Matrix in Heart Disease: Lessons from the Drosophila Genetic Model.Veterinary sciences · 2017Review
- Attenuation of neointimal formation with netrin-1 and netrin-1 preconditioned endothelial progenitor cells.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Article
- The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy.Nature medicine · 2016Article
- Identification of gene signatures regulated by carvedilol in mouse heart.Physiological genomics · 2015Article
- Potential therapeutics for myocardial ischemia-reperfusion injury. Focus on "Induction of cardioprotection by small netrin-1-derived peptides".American journal of physiology. Cell physiology · 2015Article
- Induction of cardioprotection by small netrin-1-derived peptides.American journal of physiology. Cell physiology · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Deleted in colorectal cancer (DCC), a large transmembrane receptor of netrin-1, is critical for mediating netrin-1's cardioprotective function. In the present study we investigated novel mechanisms underlying netrin-1-induced, rapid, and feed-forward up-regulation of DCC, which is believed to sustain nitric oxide (NO) production to potentiate cardioprotection. Intriguingly, NO markedly reduced expression of the E3 ubiquitin ligase seven in absentia homolog (SIAH) that is specific for regulation of protesome-dependent DCC degradation, resulting in accumulation of DCC. The two SIAH isoforms compensate for each other when one is repressed; inhibition of both SIAH1 and SIAH2 using combined siRNAs significantly reduced infarct size while improving cardiac function after ischemia/reperfusion injury of the heart. This effect was absent in DCC-deficient mice. Moreover, in vivo RNAi inhibition of SIAH1/2 further augmented netrin-1's cardioprotective function. In summary, these data identify a novel therapeutic target of SIAH in facilitating NO/netrin-1-dependent cardioprotection, using the DCC receptor. Combination of netrin-1 and SIAH RNAi may prove to be a substantially effective therapy for myocardial infarction.
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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.