| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T222 |
0-144 |
Sentence |
denotes |
The genetic loss of CFTR or a decrease in its expression and/or activity due to environmental insults such as CS leads to autophagy dysfunction. |
| T223 |
145-420 |
Sentence |
denotes |
An investigation of CFTR-deficient mice or cells isolated from CF subjects revealed an intrinsic defect in autophagy in the absence of CFTR, and the mechanism of defective CFTR-mediated autophagy impairment via the ROS-TG2-Beclin-1 pathway is well established [22,42,53,150]. |
| T224 |
421-686 |
Sentence |
denotes |
Supporting studies demonstrate that autophagy augmentation restores CS-induced CFTR dysfunction, inflammatory-oxidative stress, ceramide accumulation, and COPD-emphysema pathogenesis by rescuing aggresome-bound mutant ΔF508-CFTR to the plasma membrane (PM) [22,35]. |
| T225 |
687-871 |
Sentence |
denotes |
Conversely, restoring CFTR levels by S-nitrosoglutathione (GSNO) augmentation corrects CS-induced autophagy dysfunction, inflammatory-oxidative stress and COPD-emphysema features [62]. |
| T226 |
872-1072 |
Sentence |
denotes |
These findings not only highlight the intricate relationship between CFTR and autophagy but also provide a unique therapeutic opportunity to control exacerbations and chronic lung disease progression. |
| T227 |
1073-1273 |
Sentence |
denotes |
Several reports have suggested that the inherently elevated inflammatory-oxidative stress in CF cells, primarily due to activated NFκB signaling, could be dampened by autophagy augmentation [124,160]. |
| T228 |
1274-1501 |
Sentence |
denotes |
Moreover, it’s conceivable that CFTR dysfunction leads to impaired pathogen clearance, as the autophagy-mediated degradation of both intracellular and extracellular pathogens (xenophagy) is well demonstrated [35,45,58,151,161]. |
| T229 |
1502-1717 |
Sentence |
denotes |
An alternate mechanism called LC3-associated phagocytosis (LAP) is also described, which is similar to the normal macroautophagy pathway but does not involve the formation of a double membrane autophagosome [7,162]. |
| T230 |
1718-1944 |
Sentence |
denotes |
Nonetheless, LAP assists in the processing of both intracellular and extracellular pathogens, through the recruitment of LC3 to the phagosomal membrane and subsequent delivery to lysosomes for terminal degradation [7,151,162]. |
