Evidence that CFTR is expressed in rat tracheal smooth muscle cells and contributes to bronchodilation

Vandebrouck, Clarisse; Melin, Patricia; Norez, Caroline; Robert, Renaud; Guibert, Christelle; Mettey, Yvette; Becq, Frédéric

doi:10.1186/1465-9921-7-113

Cited by 56 publications

(68 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CFTR is insensitive to DIDS [23], and this result was confirmed in the present study, suggesting that the channel observed in rat IPA may be similar to that observed in bovine pulmonary arterial smooth muscle [17]. The pharmacological profile of CFTR activation in IPA using MPB activators (MPB-91.MPB-07.MPB-80) studied with the iodide efflux and isometric tension techniques (in the present report) is similar to that previously obtained in rat or mouse aortic myocytes [6,7], epithelial cells [21] and tracheal myocytes [5]. Moreover, endothelium removal did not influence pulmonary arterial vasorelaxation in response to MPBs, a result in agreement with that previously reported for rat and mouse aorta [6,7].…”

Section: Discussionsupporting

confidence: 78%

“…The CFTR was generally regarded as specifically expressed in epithelial cells until evidence for CFTR expression in nonepithelial tissues emerged. CFTR is expressed in cardiac muscle cells [2], brain [3] and endothelia [4], and has recently been found in tracheal smooth muscle cells (SMCs) [5] and aortic SMCs of rats and mice [6,7]. Despite this CFTR expression profile, the clinical picture of patients suffering from the CFTR-related disease cystic fibrosis appears to be unrelated to cardiac, vascular and brain dysfunction.…”

mentioning

confidence: 94%

“…IPA was dissected in culture medium under sterile conditions and cut into several pieces (1-2 mm 2 ). SMCs were obtained from these explants and cultured as previously described [5]. All cells from these explants were immunostained using the monoclonal antibody anti-smooth muscle aactin (Sigma-Aldrich, Saint-Quentin Fallavier, France), whereas they were negatively labelled with the endothelial nitric oxide synthase antibody (BD Transduction Laboratories, Le Pont-de-Claix, France; data not shown), demonstrating the presence of a population of SMCs.…”

Section: Cell Culturementioning

confidence: 99%

“…Immunofluorescence study Immunofluorescent labelling of IPA SMCs using an anti-CFTR C-terminus monoclonal antibody (mouse anti-human clone 24-1; R&D Systems) with TO-PRO-3 iodide (Molecular Probes, Invitrogen Corporation, Cergy-Pontoise, France) for nuclear staining was performed as previously described [5].…”

Section: Cell Culturementioning

confidence: 99%

See 3 more Smart Citations

Expression and function of cystic fibrosis transmembrane conductance regulator in rat intrapulmonary arteries

Robert¹,

Savineau²,

Norez³

et al. 2007

European Respiratory Journal

View full text Add to dashboard Cite

The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a cyclic adenosine monophosphate (cAMP)-dependent chloride channel located mainly at the apical membrane of epithelial cells. In myocytes of pulmonary arteries, numerous chloride channels have been identified and described, but not the CFTR. Thus the presence and function of the CFTR was investigated in rat intrapulmonary arteries.CFTR expression, localisation and function were analysed in cultured smooth muscle cells using Reverse transcriptase (RT)-PCR and immunoprecipitation followed by protein kinase A phosphorylation, immunolocalisation and an iodide efflux assay, respectively. The role of the CFTR in pulmonary vasoreactivity was determined in arterial rings using an organ bath system.RT-PCR and immunoprecipitation analyses, as well as the immunolocalisation study, revealed the expression of CFTR gene transcripts and protein. The iodide efflux assay showed the existence of functional cAMP-, calcium-and volume-dependent chloride channels. Furthermore, the following effects were found: 1) inhibition of forskolin/genistein-activated iodide efflux by glibenclamide, diphenylamine-2-carboxylic acid and CFTR-specific inhibitor (CFTRinh)-172; 2) activation of iodide efflux by the benzoquinolizinium derivative CFTR activators MPB-07 and MPB-91; and 3) inhibition of MPB-dependent efflux by CFTRinh-172. Finally, CFTR activators induced concentration-dependent vasorelaxation in rings preconstricted with phenylephrine, in the presence or absence of endothelium.The present results are the first to reveal functional cyclic adenosine monophosphate-regulated cystic fibrosis transmembrane conductance regulator contributing to endothelium-independent vasorelaxation in rat intrapulmonary arterial myocytes.

show abstract

Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 94%

Section: Cell Culturementioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

See 2 more Smart Citations

Expression and function of cystic fibrosis transmembrane conductance regulator in rat intrapulmonary arteries

Robert¹,

Savineau²,

Norez³

et al. 2007

European Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…The ex situ organ-bath technique is commonly used to determine vasomotor function of isolated blood vessels (23)(24)(25). In the present work, first and second divisions of the renal artery were dissected and cut into 3-mm-long rings.…”

Section: Ex Situ Vascular Function Studymentioning

confidence: 99%

Mechanistic Analysis of Nonoxygenated Hypothermic Machine Perfusion’s Protection on Warm Ischemic Kidney Uncovers Greater eNOS Phosphorylation and Vasodilation

Chatauret

Coudroy

Delpech

et al. 2014

American Journal of Transplantation

View full text Add to dashboard Cite

Protection of endothelial cell function may explain the benefits of nonoxygenated hypothermic machine perfusion (MP) for marginal kidney preservation. However, this hypothesis remains to be tested with a preclinical model. We postulated that MP protects the nitric oxide (NO) signaling pathway, altered by static cold storage (CS), and improves renal circulation recovery compared to CS. The endothelium releases the vasodilator NO in response to flow via either increased endothelial NO synthase (eNOS) expression (KLF2-dependent) or activation of eNOS by phosphorylation (via Akt, PKA or AMPK). Using a porcine model of kidney transplantation, including 1 h of warm ischemia and preserved 24 h by CS or MP (n ¼ 5), we reported that MP did not alter the cortical levels of KLF2 and eNOS at the end of preservation, but significantly increased eNOS activating phosphorylation compared to CS. eNOS phosphorylation appeared AMPK-dependent and was concomitant to an increased NO-dependent vasodilation of renal arteries measured, ex situ, at the end of preservation. In vivo, laser Doppler showed that cortical microcirculation was improved at reperfusion in MP kidneys. In conclusion, we demonstrate for the first time, in a large-animal model, that MP protects the NO signaling pathway, confirming the value of MP for marginal kidney preservation.Abbreviations: Akt, protein kinase B; AMPKa, 5 0 -adenosine monophosphate-activated protein kinase alpha; ANOVA, analysis of variance; CS, cold storage; CTL, control; DCD, donation after circulatory death; eNOS, endothelial nitric oxide synthase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; iNOS, inducible nitric oxide synthase; KLF2, Kruppel-like factor 2; L19, ribosomal protein L19; L-NAME, NGnitro-L-arginine methyl ester; MP, machine perfusion; MPS, machine perfusion solution; NO, nitric oxide; PKA, protein kinase A; RPLPO, ribosomal phosphoprotein large P0 subunit; RT-qPCR, reverse transcriptase quantitative polymerase chain reaction; SEM, standard error of the mean; UW, University of Wisconsin; WI-60, 1 h warm ischemia

show abstract

Cystic fibrosis transmembrane conductance regulator in human muscle: Dysfunction causes abnormal metabolic recovery in exercise

Lamhonwah

Bear

Huan

et al. 2010

Annals of Neurology

View full text Add to dashboard Cite

show abstract

Evidence that CFTR is expressed in rat tracheal smooth muscle cells and contributes to bronchodilation

Cited by 56 publications

References 40 publications

Expression and function of cystic fibrosis transmembrane conductance regulator in rat intrapulmonary arteries

Expression and function of cystic fibrosis transmembrane conductance regulator in rat intrapulmonary arteries

Mechanistic Analysis of Nonoxygenated Hypothermic Machine Perfusion’s Protection on Warm Ischemic Kidney Uncovers Greater eNOS Phosphorylation and Vasodilation

Cystic fibrosis transmembrane conductance regulator in human muscle: Dysfunction causes abnormal metabolic recovery in exercise

Contact Info

Product

Resources

About