Morrison, Cameron B. published the artcileTreatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties via hydration, Product Details of C18H10F3NO3S2, the publication is European Respiratory Journal (2022), 59(2), 2100185, database is CAplus and MEDLINE.
Cystic fibrosis (CF) is characterised by the accumulation of viscous adherent mucus in the lungs. While several hypotheses invoke a direct relationship with cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction (i.e. acidic airway surface liquid (ASL) pH, low bicarbonate (HCO3-) concentration, airway dehydration), the dominant biochem. alteration of CF mucus remains unknown. We characterised a novel cell line (CFTR-KO Calu3 cells) and the responses of human bronchial epithelial (HBE) cells from subjects with G551D or F508del mutations to ivacaftor and elexacaftor-tezacaftor-ivacaftor. A spectrum of assays such as short-circuit currents, quant. PCR, ASL pH, Western blotting, light scattering/refractometry (size-exclusion chromatog. with inline multi-angle light scattering), SEM, percentage solids and particle tracking were performed to determine the impact of CFTR function on mucus properties. Loss of CFTR function in Calu3 cells resulted in ASL pH acidification and mucus hyperconcn. (dehydration). Modulation of CFTR in CF HBE cells did not affect ASL pH or mucin mRNA expression, but decreased mucus concentration, relaxed mucus network ultrastructure and improved mucus transport. In contrast with modulator-treated cells, a large fraction of airway mucins remained attached to naive CF cells following short apical washes, as revealed by the use of reducing agents to remove residual mucus from the cell surfaces. Extended hydration, but not buffers alkalised with sodium hydroxide or HCO3-, normalized mucus recovery to modulator-treated cell levels. These results indicate that airway dehydration, not acidic pH and/or low [HCO3-], is responsible for abnormal mucus properties in CF airways and CFTR modulation predominantly restores normal mucin entanglement.
European Respiratory Journal published new progress about 307510-92-5. 307510-92-5 belongs to thiazolidine, auxiliary class Membrane Transporter/Ion Channel,CFTR, name is 4-((4-Oxo-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-5-ylidene)methyl)benzoic acid, and the molecular formula is C18H10F3NO3S2, Product Details of C18H10F3NO3S2.
Referemce:
https://en.wikipedia.org/wiki/Thiazolidine,
Thiazolidine – ScienceDirect.com