OBJECTIVES: Exosomes are 50-90nm extracellular membrane particles that may mediate trans-cellular communication between cells and tissues. We have reported that human urinary exosomes contain miRNA that are biomarkers for salt sensitivity and inverse salt sensitivity of blood pressure. This study examines exosomal transfer between cultured human renal proximal tubule cells (RPTCs) and from RPTCs to human distal tubule and collecting duct cells. DESIGN AND METHODS: For RPTC-to-RPTC exosomal transfer, we utilized 5 RPTC lines producing exosomes that were fluorescently labeled with exosomal-specific markers CD63-EGFP or CD9-RFP. Transfer between RPTCs was demonstrated by co-culturing CD63-EGFP and CD9-RFP stable clones and performing live confocal microscopy. For RPTC-to-distal segment exosomal transfer, we utilized 5 distal tubule and 3 collecting duct immortalized cell lines. RESULTS: Time-lapse videos revealed unique proximal tubule cellular uptake patterns for exosomes and eventual accumulation into the multivesicular body. Using culture supernatant containing exosomes from 3 CD9-RFP and 2 CD63-EGFP RPTC cell lines, all 5 distal tubule cell lines and all 3 collecting duct cell lines showed exosomal uptake as measured by microplate fluorometry. Furthermore, we found that RPTCs stimulated with fenoldopam (dopamine receptor agonist) had increased production of exosomes, which upon transfer to distal tubule and collecting duct cells, reduced the basal reactive oxygen species (ROS) production rates in those recipient cells. CONCLUSION: Due to the complex diversity of exosomal contents, this proximal-to-distal vesicular inter-nephron transfer may represent a previously unrecognized trans-renal communication system.
OBJECTIVES: Exosomes are 50-90nm extracellular membrane particles that may mediate trans-cellular communication between cells and tissues. We have reported that human urinary exosomes contain miRNA that are biomarkers for salt sensitivity and inverse salt sensitivity of blood pressure. This study examines exosomal transfer between cultured human renal proximal tubule cells (RPTCs) and from RPTCs to human distal tubule and collecting duct cells. DESIGN AND METHODS: For RPTC-to-RPTC exosomal transfer, we utilized 5 RPTC lines producing exosomes that were fluorescently labeled with exosomal-specific markers CD63-EGFP or CD9-RFP. Transfer between RPTCs was demonstrated by co-culturing CD63-EGFP and CD9-RFP stable clones and performing live confocal microscopy. For RPTC-to-distal segment exosomal transfer, we utilized 5 distal tubule and 3 collecting duct immortalized cell lines. RESULTS: Time-lapse videos revealed unique proximal tubule cellular uptake patterns for exosomes and eventual accumulation into the multivesicular body. Using culture supernatant containing exosomes from 3 CD9-RFP and 2 CD63-EGFP RPTC cell lines, all 5 distal tubule cell lines and all 3 collecting duct cell lines showed exosomal uptake as measured by microplate fluorometry. Furthermore, we found that RPTCs stimulated with fenoldopam (dopamine receptor agonist) had increased production of exosomes, which upon transfer to distal tubule and collecting duct cells, reduced the basal reactive oxygen species (ROS) production rates in those recipient cells. CONCLUSION: Due to the complex diversity of exosomal contents, this proximal-to-distal vesicular inter-nephron transfer may represent a previously unrecognized trans-renal communication system.
Authors: Paulina Kucharzewska; Helena C Christianson; Johanna E Welch; Katrin J Svensson; Erik Fredlund; Markus Ringnér; Matthias Mörgelin; Erika Bourseau-Guilmain; Johan Bengzon; Mattias Belting Journal: Proc Natl Acad Sci U S A Date: 2013-04-15 Impact factor: 11.205
Authors: Hadi Valadi; Karin Ekström; Apostolos Bossios; Margareta Sjöstrand; James J Lee; Jan O Lötvall Journal: Nat Cell Biol Date: 2007-05-07 Impact factor: 28.824
Authors: Adrian E Morelli; Adriana T Larregina; William J Shufesky; Mara L G Sullivan; Donna Beer Stolz; Glenn D Papworth; Alan F Zahorchak; Alison J Logar; Zhiliang Wang; Simon C Watkins; Louis D Falo; Angus W Thomson Journal: Blood Date: 2004-07-29 Impact factor: 22.113
Authors: John J Gildea; Jonathan A Israel; Andrew K Johnson; Jin Zhang; Pedro A Jose; Robin A Felder Journal: Hypertension Date: 2009-09-14 Impact factor: 10.190
Authors: Ionel Alexandru Checheriţă; Gina Manda; Mihai Eugen Hinescu; Ileana Peride; Andrei Niculae; Ştefana Bîlha; Angelica Grămăticu; Luminiţa Voroneanu; Adrian Covic Journal: Int Urol Nephrol Date: 2016-01-12 Impact factor: 2.370
Authors: Uta Erdbrügger; Charles J Blijdorp; Irene V Bijnsdorp; Francesc E Borràs; Dylan Burger; Benedetta Bussolati; James Brian Byrd; Aled Clayton; James W Dear; Juan M Falcón-Pérez; Cristina Grange; Andrew F Hill; Harry Holthöfer; Ewout J Hoorn; Guido Jenster; Connie R Jimenez; Kerstin Junker; John Klein; Mark A Knepper; Erik H Koritzinsky; James M Luther; Metka Lenassi; Janne Leivo; Inge Mertens; Luca Musante; Eline Oeyen; Maija Puhka; Martin E van Royen; Catherine Sánchez; Carolina Soekmadji; Visith Thongboonkerd; Volkert van Steijn; Gerald Verhaegh; Jason P Webber; Kenneth Witwer; Peter S T Yuen; Lei Zheng; Alicia Llorente; Elena S Martens-Uzunova Journal: J Extracell Vesicles Date: 2021-05-21