ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Treatment with quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell-cycle arrest.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Annexin A13 Protects Against Acute Kidney Injury by Inactivating TGF-β/Smad3 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SARS-CoV-2 N protein induces hypokalemia in acute kidney injury mice via ENaC-dependent mechanism.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Innate immune cells in acute and chronic kidney disease.Nature reviews. Nephrology · 2025Review
- The Role of Viral Infections in Acute Kidney Injury and Mesenchymal Stem Cell-Based Therapy.Stem cell reviews and reports · 2025Review
- Recent advances in self-targeting natural product-based nanomedicines.Journal of nanobiotechnology · 2025Review
- Smad3 Mediates Renal Fibrosis via GPX4-Dependent Ferroptosis.International journal of biological sciences · 2025Article
- Quercetin Protects Against Transmissible Gastroenteritis Virus-Induced Intestinal Inflammation by Modulating Mitophagy-Driven Mitochondrial Dysfunction.International journal of biological sciences · 2025Article
- Protective effect and mechanism of Xiaoyu Xiezhuo decoction on ischemia-reperfusion induced acute kidney injury based on gut-kidney crosstalk.Renal failure · 2024Article
- Research on the global trends of COVID-19 associated acute kidney injury: a bibliometric analysis.Renal failure · 2024Review
- Article
- The Role of Dental-derived Stem Cell-based Therapy and Their Derived Extracellular Vesicles in Post-COVID-19 Syndrome-induced Tissue Damage.Stem cell reviews and reports · 2024Review
- SARS-CoV-2 and the DNA damage response.The Journal of general virology · 2023Review
- Plant Cell-Engineered Gold Nanoparticles Conjugated to Quercetin Inhibit SARS-CoV-2 and HSV-1 Entry.International journal of molecular sciences · 2023Article
- Mechanisms and treatment of COVID-19-associated acute kidney injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- SARS-CoV-2 N protein induced acute kidney injury in diabetic db/db mice is associated with a Mincle-dependent M1 macrophage activation.Frontiers in immunology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence shows that SARS-CoV-2 can infect kidneys and cause acute kidney injury (AKI) in critically ill COVID-19 patients. However, mechanisms through which COVID-19 induces AKI are largely unknown, and treatment remains ineffective. Here, we report that kidney-specific overexpressing SARS-CoV-2 N gene can cause AKI, including tubular necrosis and elevated levels of serum creatinine and BUN in 8-week-old diabetic db/db mice, which become worse in those with older age (16 weeks) and underlying diabetic kidney disease (DKD). Treatment with quercetin, a purified product from traditional Chinese medicine (TCM) that shows effective treatment of COVID-19 patients, can significantly inhibit SARS-CoV-2 N protein-induced AKI in diabetic mice with or without underlying DKD. Mechanistically, quercetin can block the binding of SARS-CoV-2 N protein to Smad3, thereby inhibiting Smad3 signaling and Smad3-mediated cell death via the p16-dependent G1 cell-cycle arrest mechanism in vivo and in vitro. In conclusion, SARS-CoV-2 N protein is pathogenic and can cause severe AKI in diabetic mice, particularly in those with older age and pre-existing DKD, via the Smad3-dependent G1 cell-cycle arrest mechanism. Importantly, we identify that quercetin may be an effective TCM compound capable of inhibiting COVID-19 AKI by blocking SARS-CoV-2 N-Smad3-mediated cell death pathway.
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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.