ArticleDiabetes2021
FOXO1-Mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in Diabetic Kidneys.
Article in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Macrophage FOXO1 Inhibition Protects Against Hyperglycaemia-Associated Kidney Injury.Basic & clinical pharmacology & toxicology · 2026Article
- Berberine attenuates diabetic kidney injury via FOXO1/SP1-associated regulation of renal SGLT-2 expression.Chinese medicine · 2026Article
- Shedding light on the role of extracellular vesicles in renal fibrosis.Fundamental research · 2026Review
- Regulated Release of Small Extracellular Vesicles Directs Neutrophil Recruitment in Cutaneous Wound Healing.The Journal of investigative dermatology · 2026Article
- Exosome-mediated cell-cell communication: a new perspective on the mechanisms and therapeutic potential of diabetic microvascular complications.Frontiers in pharmacology · 2026Review
- Extracellular vesicles at the immune-metabolic crossroads of Hashimoto's thyroiditis and diabetes mellitus.Frontiers in immunology · 2026Review
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- Construction of a prognostic model with exosome biogenesis- and release-related genes and identification of RAB27B in immune infiltration of pancreatic cancer.Translational cancer research · 2024Article
- Tanshinone IIA Alleviates Traumatic Brain Injury by Reducing Ischemia‒Reperfusion via the miR-124-5p/FoxO1 Axis.Mediators of inflammation · 2024Article
- The biogenesis and secretion of exosomes and multivesicular bodies (MVBs): Intercellular shuttles and implications in human diseases.Genes & diseases · 2023Review
- Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Exosomes in Diabetic Kidney Disease.Kidney diseases (Basel, Switzerland) · 2023Review
- Novel Subgroups of Type 2 Diabetes Display Different Epigenetic Patterns That Associate With Future Diabetic Complications.Diabetes care · 2022Article
- Proteomics and Phosphoproteomics of Circulating Extracellular Vesicles Provide New Insights into Diabetes Pathobiology.International journal of molecular sciences · 2022Article
- Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus.Frontiers in cellular and infection microbiology · 2022Review
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8 authors at 2 institutions in 2 countries.
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Abstract
Exosomes have been implicated in diabetic kidney disease (DKD), but the regulation of exosomes in DKD is largely unknown. Here, we have verified the decrease of exosome secretion in DKD and unveiled the underlying mechanism. In Boston University mouse proximal tubule (BUMPT) cells, high-glucose (HG) treatment led to a significant decrease in exosome secretion, which was associated with specific downregulation of RAB27B, a key guanosine-5'-triphosphatase in exosome secretion. Overexpression of RAB27B restored exosome secretion in HG-treated cells, suggesting a role of RAB27B downregulation in the decrease of exosome secretion in DKD. To understand the mechanism of RAB27B downregulation, we conducted bioinformatics analysis that identified FOXO1 binding sites in the Rab27b gene promoter. Consistently, HG induced phosphorylation of FOXO1 in BUMPT cells, preventing FOXO1 accumulation and activation in the nucleus. Overexpression of nonphosphorylatable, constitutively active FOXO1 led to the upregulation of RAB27B and an increase in exosome secretion in HG-treated cells. In vivo, compared with normal mice, diabetic mice showed increased FOXO1 phosphorylation, decreased RAB27B expression, and reduced exosome secretion. Collectively, these results unveil the mechanism of exosome dysfunction in DKD where FOXO1 is phosphorylated and inactivated in DKD, resulting in RAB27B downregulation and the decrease of exosome secretion.
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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.