2026-04-28T08:53:54Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/83292024-01-15T10:40:05Zcom_10259_3592com_10259_3591com_10259.4_106com_10259_2604com_10259_3924com_10259_5086col_10259_3930col_10259_3925

Gianotti, Ambra 6c84fe61-eaab-4828-937d-bdac3fa061fe Capurro, Valeria 37ef7c40-0f16-4e31-92af-b126de551f1c 600 Delpiano, Livia 2825c426-53e5-4bd7-b0af-55d8828d006b Mielczarek, Marcin 784 600 García Valverde, María 222 600 0000-0002-3990-8388 Carreira Barral, Israel 763 600 0000-0002-4835-8752 Ludovico, Alessandra 369e0014-40de-4f45-9d64-94c578d566d3 600 Fiore, Michele 9f0bca52-d64a-4bfc-acd6-89abfaed184e 600 Baroni, Debora c33b9d33-903f-4802-ab46-cee632ac65e8 600 Moran, Óscar 15e8af37-0e8e-4441-8f3a-6a2a45cca302 600 Quesada Pato, Roberto 458 600 0000-0003-2764-7157 Caci, Emanuela 00717095-128f-48c3-8e72-c00cc09e2a85 600 2024-01-13T19:36:00Z 2024-01-13T19:36:00Z 2020 1422-0067 http://hdl.handle.net/10259/8329 10.3390/ijms21041488 1422-0067 Cystic fibrosis (CF) is a genetic disease characterized by the lack of cystic fibrosis transmembrane conductance regulator (CFTR) protein expressed in epithelial cells. The resulting defective chloride and bicarbonate secretion and imbalance of the transepithelial homeostasis lead to abnormal airway surface liquid (ASL) composition and properties. The reduced ASL volume impairs ciliary beating with the consequent accumulation of sticky mucus. This situation prevents the normal mucociliary clearance, favouring the survival and proliferation of bacteria and contributing to the genesis of CF lung disease. Here, we have explored the potential of small molecules capable of facilitating the transmembrane transport of chloride and bicarbonate in order to replace the defective transport activity elicited by CFTR in CF airway epithelia. Primary human bronchial epithelial cells obtained from CF and non-CF patients were differentiated into a mucociliated epithelia in order to assess the effects of our compounds on some key properties of ASL. The treatment of these functional models with non-toxic doses of the synthetic anionophores improved the periciliary fluid composition, reducing the fluid re-absorption, correcting the ASL pH and reducing the viscosity of the mucus, thus representing promising drug candidates for CF therapy. This work was financially supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 667079 and from the Italian Cystic Fibrosis Foundation (FFC no. CP/2012 with the contribution of ‘Delegazione FFC di Verona and Imola-Romagna’ and ‘Delegazione FFC di Roma’). application/pdf eng MDPI International Journal of Molecular Sciences. 2020, V. 21, n. 4, 1488 https://doi.org/10.3390/ijms21041488 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Cystic fibrosis Anionophore Bronchial epithelial cells culture Ion transport Periciliar mucus properties Medicina Salud Química orgánica Medicine Health Chemistry, Organic Small Molecule Anion Carriers Correct Abnormal Airway Surface Liquid Properties in Cystic Fibrosis Airway Epithelia info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion International Journal of Molecular Sciences 21 4 1488 THUMBNAIL Gianotti-ijms_2020.pdf.jpg Gianotti-ijms_2020.pdf.jpg IM Thumbnail image/jpeg 3296 https://riubu.ubu.es/bitstream/10259/8329/4/Gianotti-ijms_2020.pdf.jpg b3e3a9e798ace2cd44886795b7aecf8c MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/8329/3/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/8329/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL Gianotti-ijms_2020.pdf Gianotti-ijms_2020.pdf application/pdf 2225602 https://riubu.ubu.es/bitstream/10259/8329/1/Gianotti-ijms_2020.pdf 378934b1bb0ec5480db7e52195121fed MD5 1 10259/8329 oai:riubu.ubu.es:10259/8329 2024-01-15 11:40:05.28 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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