{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:31:57Z","timestamp":1784759517467,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: The prevalence of chronic kidney disease is increased in patients with cystic fibrosis (CF). The study of urinary exosomal proteins might provide insight into the pathophysiology of CF kidney disease. Methods: Urine samples were collected from 19 CF patients (among those 7 were treated by cystic fibrosis transmembrane conductance regulator (CFTR) modulators), and 8 healthy subjects. Urine exosomal protein content was determined by high resolution mass spectrometry. Results: A heatmap of the differentially expressed proteins in urinary exosomes showed a clear separation between control and CF patients. Seventeen proteins were upregulated in CF patients (including epidermal growth factor receptor (EGFR); proteasome subunit beta type-6, transglutaminases, caspase 14) and 118 were downregulated (including glutathione S-transferases, superoxide dismutase, klotho, endosomal sorting complex required for transport, and matrisome proteins). Gene set enrichment analysis revealed 20 gene sets upregulated and 74 downregulated. Treatment with CFTR modulators yielded no significant modification of the proteomic content. These results highlight that CF kidney cells adapt to the CFTR defect by upregulating proteasome activity and that autophagy and endosomal targeting are impaired. Increased expression of EGFR and decreased expression of klotho and matrisome might play a central role in this CF kidney signature by inducing oxidation, inflammation, accelerated senescence, and abnormal tissue repair. Conclusions: Our study unravels novel insights into consequences of CFTR dysfunction in the urinary tract, some of which may have clinical and therapeutic implications.<\/jats:p>","DOI":"10.3390\/ijms21186625","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T09:10:09Z","timestamp":1599729009000},"page":"6625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Urinary Exosomes of Patients with Cystic Fibrosis Unravel CFTR-Related Renal Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Sebastien","family":"Gauthier","sequence":"first","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Pranke","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0530-1737","authenticated-orcid":false,"given":"Vincent","family":"Jung","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151, 75015 Paris, France"},{"name":"Proteomics Platform Necker, Structure F\u00e9d\u00e9rative de Recherche Necker, 75015 Paris, France"},{"name":"INSERM US24\/CNRS UMS3633, 75015 Paris, France"},{"name":"Facult\u00e9 de M\u00e9decine, Paris Descartes, Universit\u00e9 de Paris, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1535-7515","authenticated-orcid":false,"given":"Loredana","family":"Martignetti","sequence":"additional","affiliation":[{"name":"Bioinformatics, Biostatistics, Epidemiology and Computational Systems, Institut Curie, 75005 Paris, France"},{"name":"INSERM U900, 75005 Paris, France"},{"name":"CBIO Mines-ParisTech, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Stoven","sequence":"additional","affiliation":[{"name":"Bioinformatics, Biostatistics, Epidemiology and Computational Systems, Institut Curie, 75005 Paris, France"},{"name":"INSERM U900, 75005 Paris, France"},{"name":"CBIO Mines-ParisTech, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao","family":"Nguyen-Khoa","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151, 75015 Paris, France"},{"name":"Laboratoire de Biochimie G\u00e9n\u00e9rale, H\u00f4pital Necker Enfants Malades, AP-HP Centre Universit\u00e9 de Paris, 75015 Paris, France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares, Mucoviscidose et maladies de CFTR, H\u00f4pital Necker Enfants Malades, AP-HP Centre Universit\u00e9 de Paris, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Semeraro","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares, Mucoviscidose et maladies de CFTR, H\u00f4pital Necker Enfants Malades, AP-HP Centre Universit\u00e9 de Paris, 75015 Paris, France"},{"name":"Centre d\u2019Investigation Clinique, H\u00f4pital Necker Enfants Malades, AP-HP Centre Universit\u00e9 de Paris, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Hinzpeter","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6627-4264","authenticated-orcid":false,"given":"Aleksander","family":"Edelman","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4832-6793","authenticated-orcid":false,"given":"Ida Chiara","family":"Guerrera","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151, 75015 Paris, France"},{"name":"Proteomics Platform Necker, Structure F\u00e9d\u00e9rative de Recherche Necker, 75015 Paris, France"},{"name":"INSERM US24\/CNRS UMS3633, 75015 Paris, France"},{"name":"Facult\u00e9 de M\u00e9decine, Paris Descartes, Universit\u00e9 de Paris, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Sermet-Gaudelus","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, INSERM U1151, 75015 Paris, France"},{"name":"Laboratoire de Biochimie G\u00e9n\u00e9rale, H\u00f4pital Necker Enfants Malades, AP-HP Centre Universit\u00e9 de Paris, 75015 Paris, France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares, Mucoviscidose et maladies de CFTR, H\u00f4pital Necker Enfants Malades, AP-HP Centre Universit\u00e9 de Paris, 75015 Paris, France"},{"name":"Pneumo-Allergologie P\u00e9diatrique, H\u00f4pital Necker Enfants Malades, AP-HP Centre Universit\u00e9 de Paris, 75015 Paris, France"},{"name":"European Respiratory Network, ERN Lung, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00018-016-2393-9","article-title":"Cystic fibrosis: A clinical view","volume":"74","author":"Castellani","year":"2016","journal-title":"Cell. 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