Silencing of RAB3A Reshapes the Extracellular Vesicle ncRNA Landscape in Diabetic Podocytes and Uncovers miR-126-3p as a Candidate Mediator of Podocyte Injury
9 affiliations
- 1Cardiometabolic and Renal Risk Research Group, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, 46010 Valencia, Spain
- 2Service of Endocrinology and Nutrition, Hospital Clinico Universitario of Valencia, 46010 Valencia, Spain
- 3Cardiometabolic Risk and Diabetes Group, Biomedical Research Institute of Hospital Clinico de Valencia INCLIVA, 46010 Valencia, Spain
- 4Department of Medicine, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
- 5CIBERDEM (CIBER of Diabetes and Associated Metabolic Diseases), 28029 Madrid, Spain
- 6Department of Medical Sciences, University of Turin, 10126 Turin, Italy
- 7Internal Medicine Unit, Hospital Clinico Universitario, 46010 Valencia, Spain
- 8CIBEROBN (CIBER of Pathophysiology of Obesity and Nutrition), 28029 Madrid, Spain
- 9CIBERCV (CIBER of Cardiovascular Diseases), 28029 Madrid, Spain
Abstract
Diabetic nephropathy (DN) is a major cause of chronic kidney disease and end-stage renal failure, involving progressive damage to renal cells, including podocytes. Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the kidney by transporting bioactive molecules such as non-coding RNAs. Rab3A, a small GTPase involved in vesicle docking and fusion at the plasma membrane, may influence EV biogenesis and the cargo composition. This study investigated the non-coding RNA content of EVs released by podocytes following RAB3A silencing under diabetic conditions. Cultured podocytes were transfected with RAB3A-specific siRNA and exposed to high glucose concentrations. EVs were isolated from culture media and characterized using complementary techniques, and their non-coding RNA cargo was analyzed via high-throughput sequencing and validated via RT-qPCR. Our results reveal that RAB3A silencing under high-glucose conditions induced significant changes in EV-associated non-coding RNAs, including altered levels of miR-126-3p. The context-dependent regulation of miR-126-3p suggests its involvement in IRS1/PI3K-Akt signaling, potentially affecting the balance between protective and pathogenic responses in the diabetic kidney. Overall, these findings provide new insights into the role of Rab3A in shaping EV cargo during diabetic stress and highlight EV-associated non-coding RNAs as potential contributors to the pathophysiology of DN.
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BibTeX
@article{martinezarroyo2026silencing,
title = {{Silencing of RAB3A Reshapes the Extracellular Vesicle ncRNA Landscape in Diabetic Podocytes and Uncovers miR-126-3p as a Candidate Mediator of Podocyte Injury}},
author = {Olga Martinez-Arroyo and Ana Flores-Chova and Lesley Escriva and Sergio Martinez-Hervas and Cristina Grange and Benedetta Bussolati and Maria Jose Forner and Josep Redon and Raquel Cortes and Ana Ortega},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101466},
url = {https://www.mdpi.com/2218-273X/16/10/1466},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Silencing of RAB3A Reshapes the Extracellular Vesicle ncRNA Landscape in Diabetic Podocytes and Uncovers miR-126-3p as a Candidate Mediator of Podocyte Injury
AU - Olga Martinez-Arroyo
AU - Ana Flores-Chova
AU - Lesley Escriva
AU - Sergio Martinez-Hervas
AU - Cristina Grange
AU - Benedetta Bussolati
AU - Maria Jose Forner
AU - Josep Redon
AU - Raquel Cortes
AU - Ana Ortega
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101466
UR - https://www.mdpi.com/2218-273X/16/10/1466
AB - Diabetic nephropathy (DN) is a major cause of chronic kidney disease and end-stage renal failure, involving progressive damage to renal cells, including podocytes. Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the kidney by transporting bioactive molecules such as non-coding RNAs. Rab3A, a small GTPase involved in vesicle docking and fusion at the plasma membrane, may influence EV biogenesis and the cargo composition. This study investigated the non-coding RNA content of EVs released by podocytes following RAB3A silencing under diabetic conditions. Cultured podocytes were transfected with RAB3A-specific siRNA and exposed to high glucose concentrations. EVs were isolated from culture media and characterized using complementary techniques, and their non-coding RNA cargo was analyzed via high-throughput sequencing and validated via RT-qPCR. Our results reveal that RAB3A silencing under high-glucose conditions induced significant changes in EV-associated non-coding RNAs, including altered levels of miR-126-3p. The context-dependent regulation of miR-126-3p suggests its involvement in IRS1/PI3K-Akt signaling, potentially affecting the balance between protective and pathogenic responses in the diabetic kidney. Overall, these findings provide new insights into the role of Rab3A in shaping EV cargo during diabetic stress and highlight EV-associated non-coding RNAs as potential contributors to the pathophysiology of DN.
SN - 2218-273X
ER -