ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for gene out of >500 occurrences
403337 occurrences (No.43 in the rank) during 5 years in the PubMed. [cache]
198) Formoterol also inhibited the basal expression of early growth response-1, an ERK1/2-regulated gene that controls cell growth and repair in the airways.
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PMID:34341099 DOI:10.1124/molpharm.121.000294
2021 Molecular pharmacology
* β 2-Adrenoceptor Agonists Promote Extracellular Signal-Regulated Kinase 1/2 Dephosphorylation in Human Airway Epithelial Cells by Canonical, cAMP-Driven Signaling Independently of β-Arrestin 2.
- Chronic use of β 2-adrenoceptor agonists as a monotherapy in asthma is associated with a loss of disease control and an increased risk of mortality. Herein, we tested the hypothesis that β 2-adrenoceptor agonists, including formoterol, promote biased, β-arrestin (Arr) 2-dependent activation of the mitogen-activated protein kinases, ERK1/2, in human airway epithelial cells and, thereby, effect changes in gene expression that could contribute to their adverse clinical outcomes. Three airway epithelial cell models were used: the BEAS-2B cell line, human primary bronchial epithelial cells (HBEC) grown in submersion culture, and HBEC that were highly differentiated at an air-liquid interface. Unexpectedly, treatment of all epithelial cell models with formoterol decreased basal ERK1/2 phosphorylation. This was mediated by cAMP-dependent protein kinase and involved the inactivation of C-rapidly-activated fibrosarcoma, which attenuated downstream ERK1/2 activity, and the induction of dual-specificity phosphatase 1. Formoterol also inhibited the basal expression of early growth response-1, an ERK1/2-regulated gene that controls cell growth and repair in the airways. Neither carvedilol, a β 2-adrenoceptor agonist biased toward βArr2, nor formoterol promoted ERK1/2 phosphorylation in BEAS-2B cells, although β 2-adrenoceptor desensitization was compromised in ARRB2-deficient cells. Collectively, these results contest the hypothesis that formoterol activates ERK1/2 in airway epithelia by nucleating a βArr2 signaling complex; instead, they indicate that β 2-adrenoceptor agonists inhibit constitutive ERK1/2 activity in a cAMP-dependent manner. These findings are the antithesis of results obtained using acutely challenged native and engineered HEK293 cells, which have been used extensively to study mechanisms of ERK1/2 activation, and highlight the cell type dependence of β 2-adrenoceptor-mediated signaling. SIGNIFICANCE STATEMENT: It has been proposed that the adverse effects of β 2-adrenoceptor agonist monotherapy in asthma are mediated by genomic mechanisms that occur principally in airway epithelial cells and are the result of β-arrestin 2-dependent activation of ERK1/2. This study shows that β 2-adrenoceptor agonists, paradoxically, reduced ERK1/2 phosphorylation in airway epithelia by disrupting upstream rat sarcoma-C-rapidly accelerated fibrosarcoma complex formation and inducing dual-specificity phosphatase 1. Moreover, these effects were cAMP-dependent protein kinase-dependent, suggesting that β 2-adrenoceptor agonists were not biased toward β-arrestin 2 and acted via canonical, cAMP-dependent signaling.
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[frequency of next (right) word to gene]
(1)132 expression (14)5 drive (27)3 duplications (40)2 for
(2)14 *null* (15)5 editing (28)3 ontology (41)2 from
(3)12 expression, (16)5 mutations (29)3 signature (42)2 fusion,
(4)11 and (17)5 of (30)3 to (43)2 have
(5)10 encoding (18)5 regulation (31)3 which (44)2 is
(6)10 set (19)4 networks (32)2 analysis (45)2 ontologies
(7)8 in (20)4 regulatory (33)2 are (46)2 or
(8)8 that (21)4 silencing (34)2 assay, (47)2 pathways
(9)7 1 (22)4 transcription (35)2 called (48)2 profile
(10)6 interaction (23)4 transfer (36)2 cluster (49)2 promoter
(11)6 therapy (24)3 1/itaconate (37)2 delivery (50)2 sequencing
(12)6 was (25)3 co-expression (38)2 detection (51)2 sets
(13)5 Expression (26)3 coexpression (39)2 expressions (52)2 transcripts

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--- WordNet output for gene --- =>遺伝子 Overview of noun gene The noun gene has 1 sense (no senses from tagged texts) 1. gene, cistron, factor -- ((genetics) a segment of DNA that is involved in producing a polypeptide chain; it can include regions preceding and following the coding DNA as well as introns between the exons; it is considered a unit of heredity; "genes were formerly called factors") --- WordNet end ---