ライフサイエンスコーパス: CFTR

1 CFTR activation by CDCA primarily involved Ca(2+) signal

2 CFTR inhibition has a rapid impact on islet area and ins

3 CFTR loss of function in mouse or human platelets result

4 CFTR modulators have been reported to address the basic

5 CFTR mutations cause cystic fibrosis, a lethal incurable

6 Cs) from 10 CF patients and observed 20%-50% CFTR function relative to non-CF controls in differentia

7 Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulato

8 tor (CFTR) mutation, whereas the second is a CFTR knockout model.

9 have been achieved with the combination of a CFTR corrector and potentiator in people with cystic fib

10 s the age at onset of diabetes, suggesting a CFTR-agnostic treatment for a major complication of CF.

11 the lens of prior knowledge, we compiled a "CFTR Gene Set Library" from literature.

12 In the airways, CFTR plays an important role in fluid homeostasis and he

13 acological compounds interact with and alter CFTR.

14 tezacaftor/ivacaftor and/or the alternative CFTR modulator cysteamine.

15 the use of EphaGen in context of BRCA1/2 and CFTR sequencing in a series of 14 runs across 43 blood s

16 r of both pulmonary neuroendocrine cells and CFTR-rich ionocytes.

17 ort of neosynthesized E-cadherin, MMP14, and CFTR DeltaF508, three proteins whose exocytosis is sensi

18 evels of glucocorticoids to activate PKA and CFTR.

19 s unsuitable for phosphotransfer by PKA, and CFTR mutants lacking phosphorylatable serines--that PKA

20 The immature glycoforms of SLC26A9 and CFTR co-immunoprecipitated, consistent with their intera

21 ss basolateral secretin receptors and apical CFTR and pendrin.

22 ial cells, and significantly impaired apical CFTR levels in response to forskolin.

23 (MDMs) with and without clinically approved CFTR modulators ivacaftor/lumacaftor.

24 her ATP-binding cassette proteins as well as CFTR.

25 hybridization and quantitative PCR to assess CFTR mRNA expression in the lungs, immunohistochemistry

26 efitted by co-potentiators, 14 CF-associated CFTR mutations were studied in transfected cell models.

27 s that express the most common CF-associated CFTR variant, F508del-CFTR, through mechanisms that rema

28 from the CFTR2-derived relationship between CFTR genotype function and phenotype.

29 can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to

30 odulators correct the basic defect caused by CFTR mutations.

31 xpression of CFTR is negatively regulated by CFTR-associated ligand (CAL).

32 Here, we report that CS causes CFTR to be internalized in a clathrin/dynamin-dependent

33 In cells CFTR is activated through the cAMP signaling pathway, ov

34 Mutations in the ion channel CFTR that impair its folding and subsequent localization

35 One common CFTR splicing mutation is CFTR c.3718-2477C>T (3849+10 k

36 emonstrate the utility of ASOs in correcting CFTR expression and channel activity in a manner expecte

37 Here we show that defective CFTR function in PDECs directly reduced insulin secretio

38 ttern and function was restored in DeltaF508 CFTR when cells were cultured at 28 degrees C but only i

39 The most common mutant, DeltaF508-CFTR, undergoes proteasomal degradation, extinguishing i

40 ng of DeltaY512-CFTR, like that of DeltaF508-CFTR, was greatly improved by low-temperature culture at

41 chemical interventions that rescue DeltaF508-CFTR and also re-analyzed public datasets characterizing

42 een identified to partially rescue DeltaF508-CFTR function yet remain poorly understood.

43 of DNAJB9 is sufficient to rescue DeltaF508-CFTR in vitro and in vivo, suggesting that DNAJB9 may be

44 tingly, only protein processing of DeltaY512-CFTR, like that of DeltaF508-CFTR, was greatly improved

45 ulti-DDM to assess the efficacy of different CFTR-modulating drugs in human airway epithelial cells d

46 ent approaches--an ATP analog that can drive CFTR channel gating but is unsuitable for phosphotransfe

47 n CF, and we hypothesized that dysfunctional CFTR in platelets, which are key participants in immune

48 For G542X- and E60X-CFTR, the only mechanism capable of generating functiona

49 tiation of translation were detected in E60X-CFTR.

50 rough in the development of highly effective CFTR-directed therapeutics, now applicable for up to 90%

51 (CF) is a genetic disorder of the epithelial CFTR apical chloride channel resulting in multi-organ ma

52 pithelium, more than one cell type expresses CFTR and the molecular mechanisms controlling its transc

53 Loss of either site extinguished CFTR expression and abolished long-range interactions be

54 F508del CFTR correctors induced Nrf2 nuclear translocation, Nrf2

55 , which increased wild-type (WT) and F508del CFTR biogenesis in CFBE airway cells.

56 PIAS4 knockdown reduced WT and F508del CFTR expression by 40-50%, suggesting a physiological ro

57 Here we report that approved F508del CFTR correctors VX809/VX661 recover diminished Nrf2 func

58 strate that sufficient modulation of F508del CFTR function corrects Nrf2 dysfunction in CF.

59 endogenous ubiquitin conjugation to F508del CFTR by ~50% and blocked the impact of RNF4 on mutant CF

60 ing the phenylalanine 508 deletion (F508del) CFTR variant as well as the over 2000 CF-associated vari

61 F508del-CFTR is misfolded and prematurely degraded.

62 based therapy for CF, improving both F508del-CFTR maturation and function by restoring defective auto

63 xt evaluated whether Rpl12-corrected F508del-CFTR could be further enhanced with concomitant pharmaco

64 t laboratories failed to demonstrate F508del-CFTR correction by Talpha-1.

65 thelial cells (pHBEs) homozygous for F508del-CFTR but not in non-CF pHBEs, suggesting that F508del-CF

66 12 depletion significantly increased F508del-CFTR steady-state expression, interdomain assembly, and

67 Mechanistically, F508del-CFTR modulation restored Nrf2 phosphorylation and its in

68 We monitor F508del-CFTR, the most common CF-causing variant, and confirm re

69 CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where F508del is the deletion of the phenylalanine

70 ncement of pharmacologically rescued F508del-CFTR by arginine-dependent, nitric oxide signaling throu

71 ide improves the function of rescued F508del-CFTR.

72 not in non-CF pHBEs, suggesting that F508del-CFTR enhances proteasomal SLC26A9 degradation.

73 t common CF-associated CFTR variant, F508del-CFTR, through mechanisms that remain incompletely unders

74 al SLC26A9 expression increased when F508del-CFTR trafficking was partially corrected by low temperat

75 esults should be considered in campaigns for CFTR potentiator discovery, and may enable the expansion

76 iver an essential cargo for lumen formation, CFTR (cystic fibrosis transmembrane conductance regulato

77 ing a helical-hairpin construct derived from CFTR's transmembrane (TM) helices 3 and 4 (TM3/4) and th

78 escue CFTR function in some minimal function CFTR mutants.

79 the read-through proteins of E60X- and G542X-CFTR demonstrated that both mutations have a single-chan

80 h protein is functional with E60X- and G542X-CFTR, although abundant N-terminus truncated proteins du

81 uing the gating defect of F508del- and G551D-CFTR and a promising in vitro druglike profile.

82 Unlike when phosphorylation happens, CFTR activation by PKA binding is completely reversible.

83 the mammalian protein, thereby highlighting CFTR's critical role in regulating epithelial ion transp

84 rescue of mutant CFTR, and insights into how CFTR dysfunction impairs key host defense mechanisms, su

85 However, CFTR modulators approved for use to date are highly expe

86 cryo-electron microscopy structures of human CFTR in complex with potentiators: one with the U.S.

87 (Cftr KO) mouse expressing mutants of human CFTR would advance in vivo testing of new modulators.

88 hods: In this study, we describe a humanized-CFTR rat expressing the G551D variant obtained by zinc f

89 de functional correction of Class II and III CFTR variants, restoring cell surface chloride channel a

90 PIAS4 increased immature CFTR threefold and doubled expression of mature CFTR, de

91 residues from positions 503 to 513 impaired CFTR maturation.

92 These results implicate CFTR activation in the colon as a major prosecretory mec

93 Changes in CFTR activity resulted in pressure and/or volume changes

94 rtant to elucidate how mutational defects in CFTR lead to its impairment and how pharmacological comp

95 In collecting ducts in CFTR knockout mice, baseline pendrin activity was signif

96 that DNAJB9 may be a rate-limiting factor in CFTR ERAD pathway.

97 reatment results in long-term improvement in CFTR activity in hBE cells, as demonstrated by a recover

98 Increases in CFTR activity resulted in increased E-cadherin forces, i

99 Increases in CFTR chloride secretion also induced YAP signaling and c

100 Modest increases in CFTR function related to differing genotypes were associ

101 hich was reduced by ~70% by (R)-BPO-27 or in CFTR-deficient mice.

102 concentration and lung function reported in CFTR modulator trials were compared with function-phenot

103 y 40-50%, suggesting a physiological role in CFTR biogenesis.

104 ional adaptability of TM helical segments in CFTR.

105 nhances other macrophage functions including CFTR-mediated ion efflux.

106 ly, VX-809 treatment significantly increased CFTR's co-localization with the basolateral membrane in

107 Strikingly, increasing CFTR activity was sufficient to block EMT.

108 ongenetic, CF-like sheep model, ewes inhaled CFTR(inh)172 and neutrophil elastase for 3 days, which r

109 CS exposure also inhibits CFTR, leading to the decreased anion secretion/hydration

110 One common CFTR splicing mutation is CFTR c.3718-2477C>T (3849+10 kb C>T), which creates a ne

111 so partially restores folding of full-length CFTR.

112 the lungs, immunohistochemistry to localize CFTR protein in the airways, and histopathologic assessm

113 teroids from MYO5B(P663L) piglets maintained CFTR on apical membranes, like tissues from control pigs

114 R threefold and doubled expression of mature CFTR, detected by biochemical and functional assays.

115 (R)-roscovitine also increased MDM CFTR function compared to tezacaftor/ivacaftor treatment

116 employ HIOs generated in this way to measure CFTR function using cystic fibrosis patient-derived iPSC

117 Methods: CFTR function assigned to 226 unique CFTR genotypes was

118 Here, we show that in normal mice CFTR is located within the cells and also at the apical

119 ycystic kidney disease (pkd1)-knockout mice, CFTR was located at the plasma membrane, consistent with

120 clinical use in CF patients bearing multiple CFTR mutations.

121 cantly restore channel activity for multiple CFTR variants.

122 ulator cysteamine, since no rescue of mutant CFTR function was detected following treatment with cyst

123 cations for pharmacological rescue of mutant CFTR, and insights into how CFTR dysfunction impairs key

124 50% and blocked the impact of RNF4 on mutant CFTR disposal.

125 alogues determine the fates of WT and mutant CFTRs, and they suggest that a paralogue switch during b

126 tion 508, the most common CF-causing mutant)-CFTR, knockdown of DNAJB9 by siRNA increased their expre

127 Rationale: Enhancing non-CFTR (cystic fibrosis transmembrane conductance regulato

128 Notably, CFTR potentiators used to treat cystic fibrosis effectiv

129 ts before and after treatment with the novel CFTR modulator drug, lumacaftor-ivacaftor.

130 l for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator).Objectives

131 thelia recapitulates the expected absence of CFTR activity, which was restored with ivacaftor.

132 erexpression of beta-ENaC, in the absence of CFTR dysfunction, increased NLRP3-mediated inflammation,

133 nsight may greatly facilitate assessments of CFTR modulator efficacy in individual patients.

134 cular defects caused by different classes of CFTR mutations, implications for pharmacological rescue

135 g a new chemotype to the existing classes of CFTR potentiators.

136 thermore, our data uncover a conformation of CFTR, involving detachment of NBD1 from the transmembran

137 We found that deletion of CFTR in platelets produced exaggerated acute lung inflam

138 CF caused by mutations in the NBD2 domain of CFTR.

139 upport the potential therapeutic efficacy of CFTR inhibition in bile acid-associated diarrheas.

140 Membrane expression of CFTR is negatively regulated by CFTR-associated ligand (

141 a as a key activator of airway expression of CFTR, likely through occupancy at this CRE and the gene

142 eveloped: correctors that improve folding of CFTR and potentiators that recover the function of CFTR.

143 nd potentiators that recover the function of CFTR.

144 nt G551D could be used to test the impact of CFTR modulators on pathophysiologic development and corr

145 helia via a mechanism that is independent of CFTR and is therefore independent of genotype.

146 and enhances mucus clearance independent of CFTR function.

147 Inhibition of CFTR-mediated intestinal chloride secretion as potential

148 Furthermore, the rapid internalization of CFTR is dependent on CFTR dephosphorylation by calcineur

149 ssay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences

150 Lack of CFTR function and Stx17 and loss of CFTR-Stx17 interacti

151 The results suggest two levels of CFTR regulation in cells: irreversible through phosphory

152 These data demonstrate that loss of CFTR function may predispose patients to experience depr

153 Lack of CFTR function and Stx17 and loss of CFTR-Stx17 interaction impairs bacterial clearance.

154 Here, we found that proper maturation of CFTR is dependent on cross-talk between phosphorylation

155 n the trafficking and function of a panel of CFTR variants.

156 anding of the molecular (patho)physiology of CFTR, but also infer therapeutic strategies for differen

157 d to augment phagocytosis in the presence of CFTR modulators.

158 To investigate the range of CFTR mutations benefitted by co-potentiators, 14 CF-asso

159 tation, E217G, located in the loop region of CFTR's membrane-spanning domain.

160 ulator therapy showed partial restoration of CFTR function in platelets, which may be a convenient ap

161 letely or partially remove the C-terminus of CFTR at the same time as keeping an intact NBD2 (i.e. D1

162 TR, whose PTC is closer to the C-terminus of CFTR, suggest the presence of both C-terminus truncated

163 ion is followed by retrograde trafficking of CFTR to the endoplasmic reticulum.

164 n the Clinical and Functional Translation of CFTR (CFTR2) project.

165 that a rat expressing a humanized version of CFTR and harboring the ivacaftor-sensitive variant G551D

166 The oldest CFTR ortholog identified is from dogfish shark, which re

167 mediated effects were partially dependent on CFTR and the TRPC6 channel.

168 apid internalization of CFTR is dependent on CFTR dephosphorylation by calcineurin, a protein phospha

169 ections to genes with established effects on CFTR trafficking and function and suggested novel roles

170 Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug ac

171 vealed heterogenous effects of these PTCs on CFTR function.

172 ylatable serines--that PKA efficiently opens CFTR channels through simple binding, under conditions t

173 an effect absent in mice lacking pendrin or CFTR.

174 f VX-770 to CF patients bearing ultra-orphan CFTR mutations.

175 In the pancreas, CFTR abnormality results in abnormally viscous secretion

176 therapeutic implementation of pharmacologic CFTR modulators have renewed the field's focus on develo

177 e previously reported that rescued Phe508del-CFTR (rPhe508del) can be retained at the cell surface by

178 CF combination therapies restoring Phe508del-CFTR function.

179 minimal function genotypes, in whom previous CFTR modulator regimens were ineffective.

180 that the reduced open probability in Q1412X-CFTR is the result of a disruption of the function of th

181 vestigations of the gating deficit in Q1412X-CFTR suggest that the reduced open probability in Q1412X

182 antly enhance the overall function of Q1412X-CFTR provides the conceptual basis for the treatment of

183 CF subjects receiving CFTR modulator therapy showed partial restoration of CFT

184 d by mutations of CF transmembrane receptor (CFTR) - a chloride channel present at the surface of epi

185 with CF transmembrane conductance regulator (CFTR) along with transcription factors that have binding

186 ibrosis transmembrane conductance regulator (CFTR) and the epithelial sodium channel (ENaC).

187 ibrosis transmembrane conductance regulator (CFTR) and TMEM16A (anoctamin 1), drives cyst enlargement

188 ibrosis Transmembrane Conductance Regulator (CFTR) anion channel is essential for epithelial salt-wat

189 ibrosis transmembrane conductance regulator (CFTR) anion channels produced submucosal gland mucus tha

190 ibrosis transmembrane conductance regulator (CFTR) associated with a severe form of cystic fibrosis (

191 is (CF) transmembrane conductance regulator (CFTR) at the apical membranes of epithelial cells have n

192 is (CF) transmembrane conductance regulator (CFTR) chloride channel has been argued to be critical fo

193 the CF transmembrane conductance regulator (CFTR) chloride channel.

194 ibrosis transmembrane conductance regulator (CFTR) compromise epithelial HCO(3)(-) and Cl(-) secretio

195 ibrosis transmembrane conductance regulator (CFTR) degradation is initiated by Hsp27, which cooperate

196 ibrosis transmembrane conductance regulator (CFTR) expressed on endo(sarco)plasmic reticulum.

197 ibrosis transmembrane conductance regulator (CFTR) expression, previously shown to be integral to pha

198 ibrosis Transmembrane Conductance Regulator (CFTR) function in vivo in light of recent therapeutic de

199 the CF transmembrane conductance regulator (CFTR) gene, a cyclic Adenosine MonoPhosphate (cAMP)-depe

200 the CF transmembrane conductance regulator (CFTR) gene, encoding an anion channel that conducts chlo

201 ibrosis transmembrane conductance regulator (CFTR) gene, encoding for a chloride ion channel.

202 the CF transmembrane conductance regulator (CFTR) gene, resulting in chronic bacterial lung infectio

203 ibrosis Transmembrane Conductance Regulator (CFTR) gene.

204 ibrosis transmembrane conductance regulator (CFTR) gene.

205 ibrosis transmembrane conductance regulator (CFTR) have distinct effects on nascent polypeptides.

206 ibrosis transmembrane conductance regulator (CFTR) in urinary HCO(3) (-)excretion and applied it in t

207 ibrosis transmembrane conductance regulator (CFTR) is a chloride channel central to the development o

208 ibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a ke

209 ibrosis transmembrane conductance regulator (CFTR) is an apical membrane anion channel that is widely

210 ibrosis transmembrane conductance regulator (CFTR) is an ion channel protein that is defective in ind

211 ibrosis transmembrane-conductance regulator (CFTR) is largely unknown.

212 ibrosis transmembrane conductance regulator (CFTR) is mutated in CF, and we hypothesized that dysfunc

213 ibrosis transmembrane conductance regulator (CFTR) modulators correct the basic defect caused by CFTR

214 508) CF transmembrane conductance regulator (CFTR) mutation, whereas the second is a CFTR knockout mo

215 ibrosis transmembrane conductance regulator (CFTR) plays in platelet-related inflammation.

216 ibrosis Transmembrane Conductance Regulator (CFTR) protein.

217 ibrosis transmembrane conductance regulator (CFTR), reduces cyst growth.

218 ibrosis transmembrane conductance regulator (CFTR), should reduce fluid secretion into the intestinal

219 ibrosis transmembrane conductance regulator (CFTR), which are likely to affect the natural trajectory

220 the CF transmembrane conductance regulator (CFTR), with approximately 90% of patients harboring at l

221 ibrosis transmembrane conductance regulator (CFTR)-rich ionocytes, and immune cells(1,2).

222 ibrosis transmembrane conductance regulator (CFTR).

223 ibrosis transmembrane conductance regulator (CFTR).

224 ibrosis transmembrane conductance regulator (CFTR).

225 the cystic fibrosis transmembrane regulator (CFTR) function in patient-specific primary epithelial ce

226 f CF but does not replicate a human-relevant CFTR (cystic fibrosis transmembrane conductance regulato

227 to treat cystic fibrosis effectively rescue CFTR function and markedly ameliorate the pathology of c

228 iators' (combination-potentiators) to rescue CFTR function in some minimal function CFTR mutants.

229 o 90% of people with CF who carry responsive CFTR mutations, including those with just a single copy

230 Measurements and Main Results: CFTR genotype function exhibited a logarithmic relations

231 t CDNs containing adenosine induced a robust CFTR-mediated chloride secretory response together with

232 cted the correlation between mild and severe CFTR gene mutation types and lipid profiles, suggesting

233 the lifetime of patients with CF; male sex, CFTR F508del homozygosity, and history of meconium ileus

234 tors for CFLD and severe CFLD were male sex, CFTR F508del homozygosity, and history of meconium ileus

235 tus, age at CFLD and severe CFLD onset, sex, CFTR genotype, history of meconium ileus, treatment with

236 CK19 stabilizes CFTR at the cell surface by limiting its endocytic pathw

237 s, in addition to their ability to stimulate CFTR function, which could contribute to improved clinic

238 We discover a specialized role of the Stx17-CFTR protein complex that is critical to prevent defecti

239 The 3272-26A>G and 3849+10kbC>T CFTR mutations alter the correct splicing of the CFTR ge

240 , treatments with two drug classes targeting CFTR-one boosting ion-channel function (potentiators) an

241 the therapeutic efficacy of drugs targeting CFTR and provides a value that is in much better agreeme

242 iant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation

243 Short-term CFTR inhibition increased blood glucose concentrations o

244 We investigated whether short-term CFTR inhibition was sufficient to impact islet morpholog

245 We conclude that CFTR dysfunction in platelets produces aberrant TRPC6-de

246 the first time, this study demonstrates that CFTR ion channel function and normal epithelial phenotyp

247 d mouse and human model systems to show that CFTR dysfunction in platelets increased calcium entry th

248 Here we show that CFTR modulators down regulate this exaggerated proinflam

249 The CFTR gene lies within an invariant topologically associa

250 The CFTR potentiator ivacaftor is suggested to improve gluco

251 retion of chloride ions, most notably by the CFTR channel, which has been suggested to establish pres

252 regions of large effect were identified: the CFTR locus in EA (rs113827944; OR = 1.84, p value = 1.2

253 covery that CF is caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulato

254 ed to changes in the open probability of the CFTR channel during exercise, resulting in a decrease in

255 pair and complete functional recovery of the CFTR channel.

256 Finally, we found that C18, an analog of the CFTR corrector compound Lumacaftor, induces almost no tr

257 The discovery of the CFTR gene in the late 1980s triggered a surge of basic r

258 mutations alter the correct splicing of the CFTR gene, generating new acceptor and donor splice site

259 PSC lines before and after correction of the CFTR mutation, demonstrating their future potential for

260 ng a two-dimensional characterization of the CFTR protein, it could better inform development of sing

261 We previously showed that inhibition of the CFTR/CAL interaction with a cell-permeable peptide impro

262 the premature termination codon (PTC) on the CFTR protein function.

263 In particular, the CFTR(-/-) rat has revealed insights into the airway mucu

264 F-causing mutations, partially restoring the CFTR function in terms of protein processing and/or chan

265 We test an ASO targeting the CFTR c.3718-2477C>T mutation and show that it effectivel

266 ecent therapeutic developments targeting the CFTR protein.

267 In patients, treatment with the CFTR modulator drug lumacaftor-ivacaftor increased the r

268 cepacia was enhanced by combination with the CFTR modulator tezacaftor/ivacaftor and/or the alternati

269 lly corrected by low temperature or with the CFTR modulator VX-809.

270 This study demonstrates that these CFTR modulator combinations have potent anti-inflammator

271 stimulation of which during cholera leads to CFTR-mediated intestinal salt-water loss.

272 Cystic fibrosis (CF), caused by mutations to CFTR, leads to severe and progressive lung disease.

273 location of SLC26A9 and its relationship to CFTR.

274 f the functional protein studied responds to CFTR modulators like GLPG1837 and Lumacaftor.

275 proach to monitoring biological responses to CFTR modulators.

276 r, where Rab11-associated vesicles transport CFTR to aid in lumen establishment.

277 st the presence of both C-terminus truncated CFTR proteins that are poorly functional and read-throug

278 Further analysis revealed that a wild-type CFTR-like PTM pattern and function was restored in Delta

279 ethods: CFTR function assigned to 226 unique CFTR genotypes was correlated with the clinical data of

280 In this study, we used CFTR as a model system to investigate the positional eff

281 r efficiently improves maturation of various CFTR mutants.

282 cal studies of these three PTCs with various CFTR modulators suggest position-dependent therapeutic s

283 hree PTC mutations, E60X-, G542X- and W1282X-CFTR revealed heterogenous effects of these PTCs on CFTR

284 Electrophysiological studies of W1282X-CFTR, whose PTC is closer to the C-terminus of CFTR, sug

285 Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many a

286 ration of a pharmacological blocker and when CFTR was fully functional.Conclusions: Enhancing the act

287 1 was able to accelerate clearance both when CFTR function was reduced by administration of a pharmac

288 uid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF).

289 orylation-dependent potentiation of wildtype CFTR and other variants also was observed in epithelial

290 nished Nrf2 function and colocalization with CFTR in CF human primary bronchial epithelia by proximit

291 Colocalizing with CFTR, SLC26A9 has been proposed as a target for the trea

292 ine-nitric oxide pathway in combination with CFTR modulators may lead to improved clinical outcomes.

293 -roscovitine are greatest when combined with CFTR modulators or cysteamine, justifying further clinic

294 ion, and immunofluorescence, concordant with CFTR correction.

295 , an autophagic SNARE protein interacts with CFTR under nutritional stress and bacterial infection an

296 se and the extent of pathology reversal with CFTR modulators.

297 ples from patients undergoing treatment with CFTR modulators including ivacaftor, lumacaftor, and tez

298 gradation threefold and stabilized mature WT CFTR at the plasma membrance.

299 verexpression stabilized both wild-type (WT)-CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where

300 rized and compared the core components of wt-CFTR- or rPhe508del-containing macromolecular complexes