FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912042923> ?p ?o ?g. }

• W2912042923 abstract "The inflammatory airway disease cystic fibrosis (CF) is characterized by airway obstruction due to mucus hypersecretion, airway plugging and bronchoconstriction. The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is dysfunctional in CF, leading to defects in epithelial transport. Although CF pathogenesis is still disputed, activation of alternative Cl- channels is assumed to improve lung function in CF. Two suitable non-CFTR Cl- channels are present in the airway epithelium, the Ca2+ activated channel TMEM16A and SLC26A9. Activation of these channels is thought to be feasible was to improve hydration of the airway mucus and to increase mucociliary clearance. Interestingly, both channels are upregulated during inflammatory lung disease. They are assumed to support fluid secretion, necessary to hydrate excess mucus and to maintain mucus clearance. During inflammation, however, TMEM16A is upregulated particularly in mucus producing cells, with only little expression in ciliated cells. Recently it was shown that knockout of TMEM16A in ciliated cells strongly compromises Cl- conductance and attenuated mucus secretion, but does not lead to a CF-like lung disease and airway plugging. Along this line, activation of TMEM16A by denufosol, a stable purinergic ligand, failed to demonstrate any benefit to CF patients. It rather induced adverse effects such as cough. A number of studies suggest that TMEM16A is essential for mucus secretion and possibly also for mucus production. Evidence is now provided for a crucial role of TMEM16A in fusion of mucus-filled granules with the apical plasma membrane and cellular exocytosis, which is due to local Ca2+ signals facilitated by TMEM16A. Taken together, TMEM16A supports fluid secretion by ciliated airway epithelial cells, but also appears to maintain excessive mucus secretion during inflammatory airway disease. Because TMEM16A also supports airway smooth muscle contraction, inhibition rather than activation of TMEM16A might be the appropriate treatment for CF lung disease, asthma and COPD. As a number of FDA-approved and well tolerated drugs have been shown to inhibit TMEM16A, evaluation in clinical trials appears timely." @default.
• W2912042923 created "2019-02-21" @default.
• W2912042923 creator A5000171105 @default.
• W2912042923 creator A5027498921 @default.
• W2912042923 creator A5029164837 @default.
• W2912042923 creator A5030022588 @default.
• W2912042923 creator A5034435017 @default.
• W2912042923 creator A5037554008 @default.
• W2912042923 creator A5072825937 @default.
• W2912042923 creator A5084103607 @default.
• W2912042923 date "2019-01-29" @default.
• W2912042923 modified "2023-10-05" @default.
• W2912042923 title "TMEM16A in Cystic Fibrosis: Activating or Inhibiting?" @default.
• W2912042923 cites W1020321495 @default.
• W2912042923 cites W1030961644 @default.
• W2912042923 cites W1498095761 @default.
• W2912042923 cites W1507559544 @default.
• W2912042923 cites W1536163743 @default.
• W2912042923 cites W1536852491 @default.
• W2912042923 cites W1571523472 @default.
• W2912042923 cites W1575808191 @default.
• W2912042923 cites W1582632624 @default.
• W2912042923 cites W1589654967 @default.
• W2912042923 cites W1607926222 @default.
• W2912042923 cites W1702654674 @default.
• W2912042923 cites W1859513094 @default.
• W2912042923 cites W1947692468 @default.
• W2912042923 cites W1966962396 @default.
• W2912042923 cites W1967510354 @default.
• W2912042923 cites W1968188734 @default.
• W2912042923 cites W1970003972 @default.
• W2912042923 cites W1970414736 @default.
• W2912042923 cites W1970912974 @default.
• W2912042923 cites W1972279565 @default.
• W2912042923 cites W1976022507 @default.
• W2912042923 cites W1981193117 @default.
• W2912042923 cites W1983664507 @default.
• W2912042923 cites W1984494027 @default.
• W2912042923 cites W1984648320 @default.
• W2912042923 cites W1984940953 @default.
• W2912042923 cites W1987211770 @default.
• W2912042923 cites W1991013623 @default.
• W2912042923 cites W1994132777 @default.
• W2912042923 cites W1996260537 @default.
• W2912042923 cites W1999185430 @default.
• W2912042923 cites W2000178601 @default.
• W2912042923 cites W2004155358 @default.
• W2912042923 cites W2005402925 @default.
• W2912042923 cites W2005599582 @default.
• W2912042923 cites W2005625563 @default.
• W2912042923 cites W2007227328 @default.
• W2912042923 cites W2007415402 @default.
• W2912042923 cites W2007589345 @default.
• W2912042923 cites W2008964034 @default.
• W2912042923 cites W2012480738 @default.
• W2912042923 cites W2012535637 @default.
• W2912042923 cites W2013399862 @default.
• W2912042923 cites W2014494673 @default.
• W2912042923 cites W2014856276 @default.
• W2912042923 cites W2016417321 @default.
• W2912042923 cites W2016650801 @default.
• W2912042923 cites W2020551068 @default.
• W2912042923 cites W2021332114 @default.
• W2912042923 cites W2022634662 @default.
• W2912042923 cites W2022941489 @default.
• W2912042923 cites W2023527252 @default.
• W2912042923 cites W2028817960 @default.
• W2912042923 cites W2035131077 @default.
• W2912042923 cites W2036275580 @default.
• W2912042923 cites W2036284350 @default.
• W2912042923 cites W2036820990 @default.
• W2912042923 cites W2038731679 @default.
• W2912042923 cites W2039252747 @default.
• W2912042923 cites W2039462910 @default.
• W2912042923 cites W2044380511 @default.
• W2912042923 cites W2049314578 @default.
• W2912042923 cites W2055144172 @default.
• W2912042923 cites W2057119680 @default.
• W2912042923 cites W2057772810 @default.
• W2912042923 cites W2060852213 @default.
• W2912042923 cites W2061044370 @default.
• W2912042923 cites W2065417952 @default.
• W2912042923 cites W2069881945 @default.
• W2912042923 cites W2071407356 @default.
• W2912042923 cites W2072103292 @default.
• W2912042923 cites W2074809514 @default.
• W2912042923 cites W2078078890 @default.
• W2912042923 cites W2078571865 @default.
• W2912042923 cites W2080134137 @default.
• W2912042923 cites W2082728971 @default.
• W2912042923 cites W2088493680 @default.
• W2912042923 cites W2089214886 @default.
• W2912042923 cites W2089942817 @default.
• W2912042923 cites W2091437674 @default.
• W2912042923 cites W2091729949 @default.
• W2912042923 cites W2091974182 @default.
• W2912042923 cites W2093305727 @default.
• W2912042923 cites W2093590110 @default.
• W2912042923 cites W2094582218 @default.
• W2912042923 cites W2095655618 @default.

• next