ArticleJournal of translational medicine2024
Aberrant expression of NEDD4L disrupts mitochondrial homeostasis by downregulating CaMKKβ in diabetic kidney disease.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Non-coding RNAs and Mitochondrial Dysfunction in Alzheimer's Disease: A Systematic Review.Molecular neurobiology · 2026Pooled it
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Therapeutic Regulation of Macrophage Polarization for Diabetic Kidney Disease by Targeted Metabolic Reprogramming.Current medical science · 2026Review
- Wulingsan alleviates cisplatin-induced acute kidney injury and inhibits renal tubular epithelial cell apoptosis in association with the CaSR/CaMKKβ/AMPK pathway.Frontiers in pharmacology · 2026Article
- Genetically prioritized mitochondrial regulators of advanced renal failure: multi-omic Mendelian randomization and biological plausibility assessment in allograft fibrosis.Frontiers in immunology · 2026Article
- CAMKK2 restored mitochondrial dynamics homeostasis to alleviate pulmonary fibrosis via AMPK/PGC-1α signaling pathway in lung fibroblasts.Molecular medicine (Cambridge, Mass.) · 2025Article
- Mitochondrial quality control in diabetes mellitus and complications: molecular mechanisms and therapeutic strategies.Cell death & disease · 2025Review
- NEDD4L induces mitochondrial dysfunction and neurodegeneration by promoting LIPT2 degradation in Huntington's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular dissection of the role of ACE2 in glucose homeostasis.Physiological reviews · 2025Review
- Therapeutic potential of targeting the NEDD4L-eEF1A1 axis in cancer therapy.Acta biochimica et biophysica Sinica · 2025Article
- Pathogenesis and Therapeutic Perspectives of Tubular Injury in Diabetic Kidney Disease: An Update.Biomedicines · 2025Review
- Exosomal NEDD4L derived from HG+oxLDL-induced vascular endothelial cells accelerates macrophage M1 polarization and oxLDL uptake by ubiquitinating IκBα and PPARγ.Cell biology and toxicology · 2025Article
- Nedd4L signaling contributes to carbon tetrachloride-induced liver fibrosis in female mice and is associated with enteric dysbacteriosis.Gastroenterology report · 2025Article
- WTAP-mediated mRedox report : communications in free radical research · 2024Article
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Authors and funding
6 authors.
Funding
Abstract
Disturbance in mitochondrial homeostasis within proximal tubules is a critical characteristic associated with diabetic kidney disease (DKD). CaMKKβ/AMPK signaling plays an important role in regulating mitochondrial homeostasis. Despite the downregulation of CaMKKβ in DKD pathology, the underlying mechanism remains elusive. The expression of NEDD4L, which is primarily localized to renal proximal tubules, is significantly upregulated in the renal tubules of mice with DKD. Coimmunoprecipitation (Co-IP) assays revealed a physical interaction between NEDD4L and CaMKKβ. Moreover, deletion of NEDD4L under high glucose conditions prevented rapid CaMKKβ protein degradation. In vitro studies revealed that the aberrant expression of NEDD4L negatively influences the protein stability of CaMKKβ. This study also explored the role of NEDD4L in DKD by using AAV-shNedd4L in db/db mice. These findings confirmed that NEDD4L inhibition leads to a decrease in urine protein excretion, tubulointerstitial fibrosis, and oxidative stress, and mitochondrial dysfunction. Further in vitro studies demonstrated that si-Nedd4L suppressed mitochondrial fission and reactive oxygen species (ROS) production, effects antagonized by si-CaMKKβ. In summary, the findings provided herein provide strong evidence that dysregulated NEDD4L disturbs mitochondrial homeostasis by negatively modulating CaMKKβ in the context of DKD. This evidence underscores the potential of therapeutic interventions targeting NEDD4L and CaMKKβ to safeguard renal tubular function in the management of DKD.
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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 Socratic graph.