Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression
ADPKD is the most common genetic renal disease, characterized by the presence of multiple cysts which, through slow and gradual growth, lead to glomerular filtration rate (GFR) decline and end-stage renal disease. Cystic growth is associated with increased intracellular levels of 3′,5′-cyclic adenos...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/13/9/1817 |
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| author | María Lucía Rosenberg Agustín Yaneff Gonzalo Manuel Ferradás Margarita Paz Villafañe Tapia Carlos Alberto Davio Nora Paula Goette Sandra Gabriela Vlachovsky Roxana Noemí Peroni Elisabet Mónica Oddo Pablo Javier Azurmendi |
| author_facet | María Lucía Rosenberg Agustín Yaneff Gonzalo Manuel Ferradás Margarita Paz Villafañe Tapia Carlos Alberto Davio Nora Paula Goette Sandra Gabriela Vlachovsky Roxana Noemí Peroni Elisabet Mónica Oddo Pablo Javier Azurmendi |
| author_sort | María Lucía Rosenberg |
| collection | DOAJ |
| description | ADPKD is the most common genetic renal disease, characterized by the presence of multiple cysts which, through slow and gradual growth, lead to glomerular filtration rate (GFR) decline and end-stage renal disease. Cystic growth is associated with increased intracellular levels of 3′,5′-cyclic adenosine monophosphate (cAMP). Extracellular vesicles (EVs) are proposed to participate in “remote sensing” by transporting different cargoes, but their relevance to ADPKD progression is poorly understood. This study aimed to determine whether cAMP is contained in urinary EVs and, if so, how total and/or EV cAMP contents participate in disease progression. Fourteen ADPKD patients, naïve for V<sub>2</sub> receptor antagonism treatment, and seven controls were studied. Progression was evaluated by estimating GFR (eGFR) and height-adjusted total kidney volume (htTKV). Fresh morning urine was collected to determine cAMP by the competitive radioligand assay. Urine EVs were isolated using an adapted centrifugation method and characterized by electron microscopy, dynamic light scanning, flow cytometry with FITC CD63 labeling, protein and RNA content, and <i>AQP2</i> and <i>GAPDH</i> mRNA detection. Total and EV cAMP was measurable in both control and patient urine samples. Total cAMP was significantly correlated with eGFR and its annual change but inversely correlated with htTKV. The cAMP-EVs showed a bimodal pattern with htTKV, increasing to ~1 L/m and falling at larger sizes. Our results demonstrate that urine cAMP correlates with ADPKD progression markers, and that its extracellular delivery by EVs could reflect the architectural disturbances of the organ. |
| first_indexed | 2024-03-10T22:32:48Z |
| format | Article |
| id | doaj.art-3a1efb60e3844e4ba46c078f80b4eab6 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T22:32:48Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-3a1efb60e3844e4ba46c078f80b4eab62023-11-19T11:36:43ZengMDPI AGLife2075-17292023-08-01139181710.3390/life13091817Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) ProgressionMaría Lucía Rosenberg0Agustín Yaneff1Gonzalo Manuel Ferradás2Margarita Paz Villafañe Tapia3Carlos Alberto Davio4Nora Paula Goette5Sandra Gabriela Vlachovsky6Roxana Noemí Peroni7Elisabet Mónica Oddo8Pablo Javier Azurmendi9Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires 1427, ArgentinaInstituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaInstituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires 1427, ArgentinaInstituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaInstituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaInstituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires 1427, ArgentinaInstituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires 1427, ArgentinaInstituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaInstituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires 1427, ArgentinaInstituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires 1427, ArgentinaADPKD is the most common genetic renal disease, characterized by the presence of multiple cysts which, through slow and gradual growth, lead to glomerular filtration rate (GFR) decline and end-stage renal disease. Cystic growth is associated with increased intracellular levels of 3′,5′-cyclic adenosine monophosphate (cAMP). Extracellular vesicles (EVs) are proposed to participate in “remote sensing” by transporting different cargoes, but their relevance to ADPKD progression is poorly understood. This study aimed to determine whether cAMP is contained in urinary EVs and, if so, how total and/or EV cAMP contents participate in disease progression. Fourteen ADPKD patients, naïve for V<sub>2</sub> receptor antagonism treatment, and seven controls were studied. Progression was evaluated by estimating GFR (eGFR) and height-adjusted total kidney volume (htTKV). Fresh morning urine was collected to determine cAMP by the competitive radioligand assay. Urine EVs were isolated using an adapted centrifugation method and characterized by electron microscopy, dynamic light scanning, flow cytometry with FITC CD63 labeling, protein and RNA content, and <i>AQP2</i> and <i>GAPDH</i> mRNA detection. Total and EV cAMP was measurable in both control and patient urine samples. Total cAMP was significantly correlated with eGFR and its annual change but inversely correlated with htTKV. The cAMP-EVs showed a bimodal pattern with htTKV, increasing to ~1 L/m and falling at larger sizes. Our results demonstrate that urine cAMP correlates with ADPKD progression markers, and that its extracellular delivery by EVs could reflect the architectural disturbances of the organ.https://www.mdpi.com/2075-1729/13/9/1817urine extracellular vesiclescystic growthADPKD progressioncyclic AMP |
| spellingShingle | María Lucía Rosenberg Agustín Yaneff Gonzalo Manuel Ferradás Margarita Paz Villafañe Tapia Carlos Alberto Davio Nora Paula Goette Sandra Gabriela Vlachovsky Roxana Noemí Peroni Elisabet Mónica Oddo Pablo Javier Azurmendi Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression Life urine extracellular vesicles cystic growth ADPKD progression cyclic AMP |
| title | Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression |
| title_full | Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression |
| title_fullStr | Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression |
| title_full_unstemmed | Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression |
| title_short | Total and Extracellular Vesicle cAMP Contents in Urine Are Associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) Progression |
| title_sort | total and extracellular vesicle camp contents in urine are associated with autosomal dominant polycystic kidney disease adpkd progression |
| topic | urine extracellular vesicles cystic growth ADPKD progression cyclic AMP |
| url | https://www.mdpi.com/2075-1729/13/9/1817 |
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