ArticleJCI insight2023
Calponin 2 regulates ketogenesis to mitigate acute kidney injury.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Genetic evidence and cross-species functional characterization implicateProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Perilipin 2 drives cisplatin-induced acute kidney injury in young but not aged kidneys.American journal of physiology. Renal physiology · 2026Article
- Optimizing Early Detection of Diabetic Kidney Disease through Synergistic Biomarkers and Serum Metabolites in Humans.Diabetes & metabolism journal · 2026Article
- Extracellular Matrix Control of Kidney Metabolism in Acute Kidney Injury and Repair.Journal of the American Society of Nephrology : JASN · 2026Article
- Ketone bodies in kidney diseases: novel insights.Frontiers in immunology · 2026Review
- Multimodal spatial transcriptomic characterization of mouse kidney injury and repair.Nature communications · 2025Article
- Single nucleus RNA-seq reveals the process from onset to chronic kidney disease in IgA nephropathy.Scientific reports · 2025Article
- Identification of druggable targets in acute kidney injury by proteome- and transcriptome-wide Mendelian randomization and bioinformatics analysis.Biology direct · 2025Article
- Metabolic Chaos in Kidney Disease: Unraveling Energy Dysregulation.Journal of clinical medicine · 2024Review
- Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos.Nature structural & molecular biology · 2024Article
- The metabolic pathway regulation in kidney injury and repair.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Calponin 2 (CNN2) is a prominent actin stabilizer. It regulates fatty acid oxidation (FAO) by interacting with estrogen receptor 2 (ESR2) to determine kidney fibrosis. However, whether CNN2 is actively involved in acute kidney injury (AKI) remains unclear. Here, we report that CNN2 was induced in human and animal kidneys after AKI. Knockdown of CNN2 preserved kidney function, mitigated tubular cell death and inflammation, and promoted cell proliferation. Distinct from kidney fibrosis, proteomics showed that the key elements in the FAO pathway had few changes during AKI, but we identified that 3-hydroxymethylglutaryl-CoA synthase 2 (Hmgcs2), a rate-limiting enzyme of endogenous ketogenesis that promotes cell self-renewal, was markedly increased in CNN2-knockdown kidneys. The production of ketone body β-hydroxybutyrate and ATP was increased in CNN2-knockdown mice. Mechanistically, CNN2 interacted with ESR2 to negatively regulate the activities of mitochondrial sirtuin 5. Activated sirtuin 5 subsequently desuccinylated Hmgcs2 to produce energy for mitigating AKI. Understanding CNN2-mediated discrete fine-tuning of protein posttranslational modification is critical to optimize organ performance after AKI.
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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.