Matches in SemOpenAlex for { <https://semopenalex.org/work/W2613307890> ?p ?o ?g. }
- W2613307890 endingPage "744" @default.
- W2613307890 startingPage "734" @default.
- W2613307890 abstract "Cystic fibrosis (CF) lung disease is caused by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) combined with hyperactivation of the epithelial sodium channel (ENaC). In the lung, ENaC is responsible for movement of sodium. Hyperactivation of ENaC, which creates an osmotic gradient that pulls fluid out of the airway, contributes to reduced airway hydration, causing mucus dehydration, decreased mucociliary clearance, and recurrent acute bacterial infections. ENaC represents a therapeutic target to treat all patients with CF independent of their underlying CFTR mutation.To investigate the in vitro and in vivo efficacy of SPX-101, a peptide mimetic of the natural regulation of ENaC activity by short palate, lung, and nasal epithelial clone 1, known as SPLUNC1.ENaC internalization by SPX-101 in primary human bronchial epithelial cells from healthy and CF donors was assessed by surface biotinylation and subsequent Western blot analysis. SPX-101's in vivo therapeutic effect was assessed by survival of β-ENaC-transgenic mice, mucus transport in these mice, and mucus transport in a sheep model of CF.SPX-101 binds selectively to ENaC and promotes internalization of the α-, β-, and γ-subunits. Removing ENaC from the membrane with SPX-101 causes a significant decrease in amiloride-sensitive current. The peptide increases survival of β-ENaC-transgenic mice to greater than 90% with once-daily dosing by inhalation. SPX-101 increased mucus transport in the β-ENaC mouse model as well as the sheep model of CF.These data demonstrate that SPX-101 promotes durable reduction of ENaC membrane concentration, leading to significant improvements in mucus transport." @default.
- W2613307890 created "2017-05-19" @default.
- W2613307890 creator A5000172570 @default.
- W2613307890 creator A5001272649 @default.
- W2613307890 creator A5008929527 @default.
- W2613307890 creator A5015740336 @default.
- W2613307890 creator A5023416614 @default.
- W2613307890 creator A5038884141 @default.
- W2613307890 creator A5057048732 @default.
- W2613307890 creator A5058249371 @default.
- W2613307890 creator A5066447096 @default.
- W2613307890 creator A5074973044 @default.
- W2613307890 date "2017-09-15" @default.
- W2613307890 modified "2023-09-24" @default.
- W2613307890 title "SPX-101 Is a Novel Epithelial Sodium Channel–targeted Therapeutic for Cystic Fibrosis That Restores Mucus Transport" @default.
- W2613307890 cites W1902231903 @default.
- W2613307890 cites W1965867102 @default.
- W2613307890 cites W1975572445 @default.
- W2613307890 cites W1978028270 @default.
- W2613307890 cites W1979040675 @default.
- W2613307890 cites W1983336470 @default.
- W2613307890 cites W1985372182 @default.
- W2613307890 cites W1985830780 @default.
- W2613307890 cites W1987815970 @default.
- W2613307890 cites W1990252413 @default.
- W2613307890 cites W1990301853 @default.
- W2613307890 cites W1991013623 @default.
- W2613307890 cites W2008277961 @default.
- W2613307890 cites W2019099644 @default.
- W2613307890 cites W2022941489 @default.
- W2613307890 cites W2024738561 @default.
- W2613307890 cites W2027500788 @default.
- W2613307890 cites W2027586786 @default.
- W2613307890 cites W2031379784 @default.
- W2613307890 cites W2032295315 @default.
- W2613307890 cites W2035131077 @default.
- W2613307890 cites W2045124875 @default.
- W2613307890 cites W2066972002 @default.
- W2613307890 cites W2071407356 @default.
- W2613307890 cites W2072684870 @default.
- W2613307890 cites W2075017474 @default.
- W2613307890 cites W2083506368 @default.
- W2613307890 cites W2102931921 @default.
- W2613307890 cites W2108047993 @default.
- W2613307890 cites W2108676410 @default.
- W2613307890 cites W2122466842 @default.
- W2613307890 cites W2135363031 @default.
- W2613307890 cites W2144248619 @default.
- W2613307890 cites W2145346414 @default.
- W2613307890 cites W2148079274 @default.
- W2613307890 cites W2150908316 @default.
- W2613307890 cites W2166796744 @default.
- W2613307890 cites W2170476499 @default.
- W2613307890 cites W2223779815 @default.
- W2613307890 cites W2312783022 @default.
- W2613307890 cites W2320394900 @default.
- W2613307890 cites W2326585024 @default.
- W2613307890 cites W2342221518 @default.
- W2613307890 cites W2413505253 @default.
- W2613307890 cites W2586167769 @default.
- W2613307890 doi "https://doi.org/10.1164/rccm.201612-2445oc" @default.
- W2613307890 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28481660" @default.
- W2613307890 hasPublicationYear "2017" @default.
- W2613307890 type Work @default.
- W2613307890 sameAs 2613307890 @default.
- W2613307890 citedByCount "47" @default.
- W2613307890 countsByYear W26133078902017 @default.
- W2613307890 countsByYear W26133078902018 @default.
- W2613307890 countsByYear W26133078902019 @default.
- W2613307890 countsByYear W26133078902020 @default.
- W2613307890 countsByYear W26133078902021 @default.
- W2613307890 countsByYear W26133078902022 @default.
- W2613307890 countsByYear W26133078902023 @default.
- W2613307890 crossrefType "journal-article" @default.
- W2613307890 hasAuthorship W2613307890A5000172570 @default.
- W2613307890 hasAuthorship W2613307890A5001272649 @default.
- W2613307890 hasAuthorship W2613307890A5008929527 @default.
- W2613307890 hasAuthorship W2613307890A5015740336 @default.
- W2613307890 hasAuthorship W2613307890A5023416614 @default.
- W2613307890 hasAuthorship W2613307890A5038884141 @default.
- W2613307890 hasAuthorship W2613307890A5057048732 @default.
- W2613307890 hasAuthorship W2613307890A5058249371 @default.
- W2613307890 hasAuthorship W2613307890A5066447096 @default.
- W2613307890 hasAuthorship W2613307890A5074973044 @default.
- W2613307890 hasConcept C114682108 @default.
- W2613307890 hasConcept C126322002 @default.
- W2613307890 hasConcept C134018914 @default.
- W2613307890 hasConcept C139770010 @default.
- W2613307890 hasConcept C142724271 @default.
- W2613307890 hasConcept C170493617 @default.
- W2613307890 hasConcept C178790620 @default.
- W2613307890 hasConcept C185592680 @default.
- W2613307890 hasConcept C18903297 @default.
- W2613307890 hasConcept C2776938444 @default.
- W2613307890 hasConcept C2777312293 @default.
- W2613307890 hasConcept C2777714996 @default.
- W2613307890 hasConcept C2778428886 @default.
- W2613307890 hasConcept C2779608910 @default.