1. Urinary- and Plasma-Derived Exosomes Reveal a Distinct MicroRNA Signature Associated With Albuminuria in Hypertension
- Author
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Josep Redon, Angela L. Riffo-Campos, Ana Ortega, Fernando Martinez, Olga Martinez-Arroyo, Dolores Olivares, Sergio Martínez-Hervás, Raquel Cortés, Javier Perez-Hernandez, E. Solaz, Felipe J. Chaves, and Daniel Perez-Gil
- Subjects
0301 basic medicine ,Male ,Down-Regulation ,030204 cardiovascular system & hematology ,Exosomes ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Paracrine signalling ,0302 clinical medicine ,microRNA ,Internal Medicine ,medicine ,Albuminuria ,Humans ,Gene Regulatory Networks ,KEGG ,Cells, Cultured ,Aged ,Kidney ,business.industry ,Podocytes ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Middle Aged ,Microvesicles ,MicroRNAs ,030104 developmental biology ,Real-time polymerase chain reaction ,medicine.anatomical_structure ,Hypertension ,Cancer research ,Female ,medicine.symptom ,business ,Transforming growth factor - Abstract
Urinary albumin excretion (UAE) is a marker of cardiovascular risk and renal damage in hypertension. MicroRNAs (miRNAs) packaged into exosomes function as paracrine effectors in cell communication and the kidney is not exempt. This study aimed to state an exosomal miRNA profile/signature associated to hypertension with increased UAE and the impact of profibrotic TGF-β1 (transforming growth factor β1) on exosomes miRNA release. Therefore, exosomes samples from patients with hypertension with/without UAE were isolated and characterized. Three individual and unique small RNA libraries from each subject were prepared (total plasma, urinary, and plasma-derived exosomes) for next-generation sequencing profiling. Differentially expressed miRNAs were over-represented in Kyoto Encyclopedia of Genes and Genomes pathways, and selected miRNAs were validated by real-time quantitative polymerase chain reaction in a confirmation cohort. Thus, a signature of 29 dysregulated circulating miRNAs was identified in UAE hypertensive subjects, regulating 21 pathways. Moreover, changes in the levels of 4 exosomes-miRNAs were validated in a confirmation cohort and found associated with albuminuria. In particular miR-26a, major regulator of TGF-β signaling, was found downregulated in both type of exosomes when compared with healthy controls and to hypertension normoalbuminurics ( P
- Published
- 2021