18 results on '"Solway, Julian"'
Search Results
2. Serum response factor function and dysfunction in smooth muscle
- Author
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Camoretti-Mercado, Blanca, Dulin, Nickolai O., and Solway, Julian
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- 2003
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3. Structural and functional abnormalities of the airways of hyperoxia-exposed immature rats
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Solway, Julian and Hershenson, Marc B.
- Subjects
Oxygen -- Health aspects -- Analysis -- Models ,Bronchial provocation tests -- Analysis -- Models -- Health aspects ,Asthma -- Models -- Analysis -- Health aspects ,Health ,Analysis ,Models ,Health aspects - Abstract
Asthma and bronchopulmonary dysplasia are prevalent diseases characterized by airway constrictor hyperresponsiveness and excessive airway smooth muscle accumulation. It is now well accepted that some alterations in airway wall architecture [...]
- Published
- 1995
4. Elevated levels of soluble humanleukocyte antigen-G in the airways are a marker for a low-inflammatory endotype of asthma.
- Author
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White, Steven R., Nicodemus-Johnson, Jessie, Laxman, Bharathi, Denner, Darcy R., Naureckas, Edward T., Hogarth, D. Kyle, Stern, Randi, Minc, Alexa, Solway, Julian, Sperling, Anne, and Ober, Carole
- Published
- 2017
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5. A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes.
- Author
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Sharma, Sunita, Zhou, Xiaobo, Thibault, Derek M., Himes, Blanca E., Liu, Andy, Szefler, Stanley J., Strunk, Robert, Castro, Mario, Hansel, Nadia N., Diette, Gregory B., Vonakis, Becky M., Jr.Adkinson, N. Franklin, Avila, Lydiana, Soto-Quiros, Manuel, Barraza-Villareal, Albino, Jr.Lemanske, Robert F., Solway, Julian, Krishnan, Jerry, White, Steven R., and Cheadle, Chris
- Abstract
Background Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. Objective We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4 + lymphocytes for association with asthma. Methods eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. Results Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3 / GSDMB variants with asthma (combined P = 2.9 × 10 −8 ). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 ( FADS2 ; P = .002), N-acetyl-α-D-galactosaminidase ( NAGA ; P = .0002), and Factor XIII, A1 ( F13A1 ; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4 + lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. Conclusions Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2 , NAGA , and F13A1 in the pathogenesis of asthma. [ABSTRACT FROM AUTHOR]
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- 2014
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6. E3 Ubiquitin Ligase Cbl-b Suppresses Proallergic T Cell Development and Allergic Airway Inflammation.
- Author
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Qiao, Guilin, Ying, Haiyan, Zhao, Yixia, Liang, Yanran, Guo, Hui, Shen, Huifeng, Li, Zhenping, Solway, Julian, Tao, Enxiang, Chiang, Y. Jeffrey, Lipkowitz, Stanley, Penninger, Josef M., Langdon, Wallace Y., and Zhang, Jian
- Abstract
Summary: E3 ubiquitin ligase Cbl-b has emerged as a gatekeeper that controls the activation threshold of the T cell antigen receptor and maintains the balance between tolerance and autoimmunity. Here, we report that the loss of Cbl-b facilitates T helper 2 (Th2) and Th9 cell differentiation in vitro. In a mouse model of asthma, the absence of Cbl-b results in severe airway inflammation and stronger Th2 and Th9 responses. Mechanistically, Cbl-b selectively associates with Stat6 upon IL-4 ligation and targets Stat6 for ubiquitination and degradation. These processes are heightened in the presence of T cell receptor (TCR)/CD28 costimulation. Furthermore, we identify K108 and K398 as Stat6 ubiquitination sites. Intriguingly, introducing Stat6 deficiency into Cblb
−/− mice abrogates hyper-Th2 responses but only partially attenuates Th9 responses. Therefore, our data reveal a function for Cbl-b in the regulation of Th2 and Th9 cell differentiation. [Copyright &y& Elsevier]- Published
- 2014
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7. Emerging targets for novel therapy of asthma.
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Gerthoffer, William T, Solway, Julian, and Camoretti-Mercado, Blanca
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ASTHMA treatment , *TASTE receptors , *PROSTAGLANDIN receptors , *TARGETED drug delivery , *BRONCHODILATOR agents , *HEAT shock proteins , *ADENOSINE monophosphate , *BRONCHOCONSTRICTION - Abstract
Highlights: [•] Bitter taste receptors (TAS2R) and EP4 prostaglandin receptors are emerging targets for new bronchodilators. [•] Heat shock protein HSP20 is a cAMP-dependent inhibitor of bronchoconstriction. [•] Rho kinase signaling is also a promising target for novel bronchodilator therapy. [•] Statins may inhibit small G-protein signaling to promote bronchodilation. [•] New epigenetic targets include histone modifying enzymes and microRNAs. [ABSTRACT FROM AUTHOR]
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- 2013
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8. Expression Cloning Identifies Transgelin (SM22) as a Novel Repressor of 92-kDa Type IV Collagenase (MMP-9) Expression.
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Nair, Rajesh R., Solway, Julian, and Boyd, Douglas D.
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GENE expression , *GENETIC regulation , *COLLAGENASES , *GENETIC vectors , *CARRIER proteins , *CELL membranes , *MESSENGER RNA , *TISSUE remodeling , *MOLECULAR cloning - Abstract
The 92-kDa gelatinase (MMP-9) expression is prerequisite for tissue remodeling in physiology and cancer. However, there are few known regulators of MMP-9 expression. Using an expression cloning strategy, we identified transgelin (SM22), a 22–25-kDa actin-binding protein localized to the cell membrane and cytoplasm, as a novel regulator of MMP-9 expression. Overexpression of a SM22 cDNA in HT1080 cells decreased MMP-9 mRNA/protein levels and diminished in vitro invasion of the latter rescued with exogenous MMP-9. Conversely, small interfering RNA-mediated knockdown of SM22 elevated MMP-9 synthesis, and uterus from SM22-null mice showed strong MMP-9 immunoreactivity compared with wild type animals. The ability of SM22 to repress MMP-9 expression required an intact amino terminus calponin homology domain. MMP-9 expression is driven by ERK signaling and SM22 targeted this pathway as evidenced by (a) the transience in MAPK activation and (b) blunted stimulation of the MMP-9 promoter by a constitutively active MEK expression vector. Progressive deletion analysis located the SM22 responsive region of the MMP-9 promoter to the proximal 90-bp region harboring an AP-1 motif subsequently implicated by site-directed mutagenesis. Furthermore, nuclear extract from the SM22 transfectants showed diminished c-Fos binding to this motif and SM22 expression reduced the activity of an AP-1-driven reporter by 75%. Thus, SM22 adds to a short list of repressors of MMP-9 expression, achieving this by reducing AP-l-dependent trans-activation of the gene by way of compromised ERK activation. Diminished transgelin expression in several cancers may thus partly account for the elevated MMP-9 expression evident in these tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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9. 2A3 and 3F9: novel lung epithelial antigens with early upregulation in hyperoxic and radiation lung injury models
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Girod, Carlos E., Hershenson, Marc B., Solway, Julian, Gilman, Laura B., and Miller, York E.
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Tumors, Radiation-induced -- Models ,Lung tumors -- Models ,Radiation injuries -- Models ,Health ,Models - Abstract
The alveolar epithelium responds to injury by upregulation of various specialized functions: proliferation and differentiation of epithelial cells, maintenance of electroyte and water balance, secretion of surfactant and associated proteins, [...]
- Published
- 1996
10. Associations between fungal and bacterial microbiota of airways and asthma endotypes.
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Sharma, Anukriti, Laxman, Bharathi, Naureckas, Edward T., Hogarth, D. Kyle, Sperling, Anne I., Solway, Julian, Ober, Carole, Gilbert, Jack A., and White, Steven R.
- Abstract
The relationship between asthma, atopy, and underlying type 2 (T2) airway inflammation is complex. Although the bacterial airway microbiota is known to differ in asthmatic patients, the fungal and bacterial markers that discriminate T2-high (eosinophilic) and T2-low (neutrophilic/mixed-inflammation) asthma and atopy are still incompletely identified. The aim of this study was to demonstrate the fungal microbiota structure of airways in asthmatic patients associated with T2 inflammation, atopy, and key clinical parameters. We collected endobronchial brush (EB) and bronchoalveolar lavage (BAL) samples from 39 asthmatic patients and 19 healthy subjects followed by 16S gene and internal transcribed spacer–based microbiota sequencing. The microbial sequences were classified into exact sequence variants. The T2 phenotype was defined by using a blood eosinophil count with a threshold of 300 cells/μL. Fungal diversity was significantly lower in EB samples from patients with T2-high compared with T2-low inflammation; key fungal genera enriched in patients with T2-high inflammation included Trichoderma species, whereas Penicillium species was enriched in patients with atopy. In BAL fluid samples the dominant genera were Cladosporium , Fusarium , Aspergillus , and Alternaria. Using generalized linear models, we identified significant associations between specific fungal exact sequence variants and FEV 1 , fraction of exhaled nitric oxide values, BAL fluid cell counts, and corticosteroid use. Investigation of interkingdom (bacterial-fungal) co-occurrence patterns revealed different topologies between asthmatic patients and healthy control subjects. Random forest models with fungal classifiers predicted asthma status with 75% accuracy for BAL fluid samples and 80% accuracy for EB samples. We demonstrate clear differences in bacterial and fungal microbiota in asthma-associated phenotypes. Our study provides additional support for considering microbial signatures in delineating asthma phenotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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11. Evidence for an IL-6–high asthma phenotype in asthmatic patients of African ancestry.
- Author
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White, Steven R., Laxman, Bharathi, Naureckas, Edward T., Hogarth, D. Kyle, Solway, Julian, Sperling, Anne I., and Ober, Carole
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- 2019
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12. An inflammation-independent contraction mechanophenotype of airway smooth muscle in asthma.
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An, Steven S., Mitzner, Wayne, Tang, Wan-Yee, Ahn, Kwangmi, Yoon, A-Rum, Huang, Jessie, Kilic, Onur, Yong, Hwan Mee, Fahey, Jed W., Kumar, Sarvesh, Biswal, Shyam, Holgate, Stephen T., Jr.Panettieri, Reynold A., Solway, Julian, and Liggett, Stephen B.
- Published
- 2016
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13. Corticosteroid therapy and airflow obstruction influence the bronchial microbiome, which is distinct from that of bronchoalveolar lavage in asthmatic airways.
- Author
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Denner, Darcy R., Sangwan, Naseer, Becker, Julia B., Hogarth, D. Kyle, Oldham, Justin, Castillo, Jamee, Sperling, Anne I., Solway, Julian, Naureckas, Edward T., Gilbert, Jack A., and White, Steven R.
- Abstract
Background The lung has a diverse microbiome that is modest in biomass. This microbiome differs in asthmatic patients compared with control subjects, but the effects of clinical characteristics on the microbial community composition and structure are not clear. Objectives We examined whether the composition and structure of the lower airway microbiome correlated with clinical characteristics of chronic persistent asthma, including airflow obstruction, use of corticosteroid medications, and presence of airway eosinophilia. Methods DNA was extracted from endobronchial brushings and bronchoalveolar lavage fluid collected from 39 asthmatic patients and 19 control subjects, along with negative control samples. 16S rRNA V4 amplicon sequencing was used to compare the relative abundance of bacterial genera with clinical characteristics. Results Differential feature selection analysis revealed significant differences in microbial diversity between brush and lavage samples from asthmatic patients and control subjects. Lactobacillus , Pseudomonas , and Rickettsia species were significantly enriched in samples from asthmatic patients, whereas Prevotella , Streptococcus , and Veillonella species were enriched in brush samples from control subjects. Generalized linear models on brush samples demonstrated oral corticosteroid use as an important factor affecting the relative abundance of the taxa that were significantly enriched in asthmatic patients. In addition, bacterial α-diversity in brush samples from asthmatic patients was correlated with FEV 1 and the proportion of lavage eosinophils. Conclusion The diversity and composition of the bronchial airway microbiome of asthmatic patients is distinct from that of nonasthmatic control subjects and influenced by worsening airflow obstruction and corticosteroid use. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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14. Maternal asthma and microRNA regulation of soluble HLA-G in the airway.
- Author
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Nicodemus-Johnson, Jessie, Laxman, Bharathi, Stern, Randi K., Sudi, Jyotsna, Tierney, Courtney N., Norwick, Lourdes, Hogarth, Douglas K., McConville, John F., Naureckas, Edward T., Sperling, Anne I., Solway, Julian, Krishnan, Jerry A., Nicolae, Dan L., White, Steven R., and Ober, Carole
- Abstract
Background: We previously reported an interaction between maternal asthma and the child's HLA-G genotype on the child's subsequent risk for asthma. The implicated single nucleotide polymorphism at +3142 disrupted a target site for the microRNA (miR)-152 family. We hypothesized that the interaction effect might be mediated by these miRs. Objective: The objective of this study was to test this hypothesis in adults with asthma who are a subset of the same subjects who participated in our earlier family-based studies. Methods: We measured soluble HLA-G (sHLA-G) concentrations in bronchoalveolar lavage fluid (n = 36) and plasma (n = 57) from adult asthmatic subjects with and without a mother with asthma, and HLA-G and miR-152 family (miR-148a, miR-148b, and miR-152) transcript levels in airway epithelial cells from the same subjects. Results: miR-148b levels were significantly increased in airway epithelial cells from asthmatic subjects with an asthmatic mother compared with those seen in asthmatic subjects without an asthmatic mother, and +3142 genotypes were associated with sHLA-G concentrations in bronchoalveolar lavage fluid among asthmatic subjects with an asthmatic mother but not among those with a nonasthmatic mother. Neither effect was observed in the plasma (sHLA-G) or white blood cells (miRNA). Conclusion: These combined results are consistent with +3142 allele–specific targeting of HLA-G by the miR-152 family and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subject's mother and the subject's genotype. Moreover, we demonstrate that the effects of maternal asthma on the gene regulatory landscape in the airways of the mother's children persist into adulthood. [Copyright &y& Elsevier]
- Published
- 2013
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15. Lysophosphatidic Acid Enhances Pulmonary Epithelial Barrier Integrity and Protects Endotoxin-induced Epithelial Barrier Disruption and Lung lnjury.
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Donghong He, Yanlin Su, Usatyuk, Peter V., Spannhake, Ernst Wm., Kogut, Paul, Solway, Julian, Natarajan, Viswanathan, and Zhao, Yutong
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LYSOPHOSPHOLIPIDS , *ENDOTOXIN analysis , *EPITHELIAL cells , *LUNG disease diagnosis , *PROTEIN kinase C , *CELL communication , *IMMUNOREGULATION , *FOCAL adhesion kinase , *CELL physiology - Abstract
Lysophosphatidic acid (LPA), a bioactive phospholipid, induces a wide range of cellular effects, including gene expression, cytoskeletal rearrangement, and cell survival. We have previously shown that LPA stimulates secretion of proand antiinflammatory cytokines in bronchial epithelial cells. This study provides evidence that LPA enhances pulmonary epithelial barrier integrity through protein kinase C (PKC) δ- and ζ-mediated E-cadherin accumulation at cell-cell junctions. Treatment of human bronchial epithelial cells (HBEpCs) with LPA increased transepithelial electrical resistance (TER) by ∼2.0-fold and enhanced accumulation of E-cadherin to the cell-cell junctions through Gαi-coupled LPA receptors. Knockdown of E-cadherin with E-cadherin small interfering RNA or pretreatment with EGTA (0.1 mM) prior to LPA (1 μM) treatment attenuated LPA-induced increases in TER in HBEpCs. Furthermore, LPA induced tyrosine phosphorylation of focal adhesion kinase (FAK) and overexpression of the FAK inhibitor, and FAK-related non-kinase-attenuatecl LPA induced increases in TER and E-cadherin accumulation at cell-cell junctions. Overexpression of dominant negative protein kinase δ and ζ attenuated LPA-induced phosphorylation of FAK, accumulation of E-cadherin at cell-cell junctions, and an increase in TER. Additionally, lipopolysaccharide decreased TER and induced E-cadherin relocalization from cell-cell junctions to cytoplasm in a dose-dependent fashion, which was restored by LPA post-treatment in HBEpCs. Intratracheal post-treatment with LPA (5 μM) reduced LPS-induced neutrophil influx, protein leak, and E-cadherin shedding in bronchoalveolar lavage fluids in a murine model of acute lung injury. These data suggest a protective role of LPA in airway inflammation and remodeling. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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16. Inhibition of Transforming Growth Factor ß-enhanced Serum Response Factor-dependent Transcription by SMAD7.
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Camoretti-Mercado, Blanca, Fernandes, Darren J., Dewundara, Samantha, Churchill, Jason, Ma, Lan, Kogut, Paul C., McConville, John F., Parmacek, Michael S., and Solway, Julian
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CELLULAR control mechanisms , *TRANSFORMING growth factors-beta , *SERUM , *GENETIC transcription , *MUSCLE cells , *TRANSFORMING growth factors , *SMOOTH muscle , *ASTHMA - Abstract
Transforming growth factor (TGF)-β is present in large amounts in the airways of patients with asthma and with other diseases of the lung. We show here that TGFβ treatment increased transcriptional activation of SM22α, a smooth muscle-specific promoter, in airway smooth muscle cells, and we demonstrate that this effect stems in part from TGFβ-induced enhancement of serum response factor (SRF) DNA binding and transcription promoting activity. Overexpression of Smad7 inhibited TGFβ-induced stimulation of SRF-dependent promoter function, and chromatin immunoprecipitation as well as co-immunoprecipitation assays established that endogenous or recombinant SRF interacts with Smad7 within the nucleus. The SRF binding domain of Smad7 mapped to the C-terminal half of the Smad7 molecule. TGFβ treatment weakened Smad7 association with SRF, and conversely the Smad7-SRF interaction was increased by inhibition of the TGFβ pathway through overexpression of a dominant negative mutant of TGFβ receptor I or of Smad3 phosphorylation-deficient mutant. Our findings thus reveal that SRF-Smad7 interactions in part mediate TGFβ regulation of gene transcription in airway smooth muscle. This offers potential targets for interventions in treating lung inflammation and asthma. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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17. Functional Characterization of Evolutionarily Conserved DNA Regions in Forkhead Box F1 Gene Locus.
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Kim, II-Man, Yan Zhou, Ramakrishna, Sneha, Hughes, Douglas E., Solway, Julian, Costa, Robert H., and Kalinichenko, Vladimir V.
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DNA , *DEOXYRIBOSE , *NUCLEIC acids , *TRANSCRIPTION factors , *GENE expression , *NUCLEOTIDE sequence , *HEREDITY , *TRANSGENIC mice , *LABORATORY mice - Abstract
The Forkhead Box f1 (Foxf1) transcription factor (previously known as HFH-8 or Freac-1) is expressed in the septum transversum and splanchnic (visceral) mesoderm and is required for proper development of gut-derived organs. Sequence comparisons of mouse and human Fox f1 genes have revealed highly conserved DNA sequences located within the -5.3-kb Foxf1 promoter region and the 400-nucleotide regulatory element located 1 kb 3′ to the Foxf1 gene (3′RE). To examine their transcriptional activity during mouse embryonic development, we generated transgenic mice in which the expression of the β-galactosidase transgene was controlled by the -2.7-kb Foxf1 promoter region, the -5.3-kb Foxf1 promoter region, or the -5.3-kb Foxf1 promoter region fused to the 3′RE. The -5.3-kb Foxf1 promoter sequences induced appropriate transgene expression in the midgut and developing intestine, whereas the -2.7-kb Foxf1 promoter region was transcriptionally inactive. Addition of 3′RE to the -5.3-kb Foxf1 promoter restored proper transgene expression in the foregut, liver, and lung mesenchyme and prevented ectopic transgene expression in the developing nervous system. Cotransfection studies demonstrated that FoxA2 protein bound to the 3′RE region (+4506/+4529 bp) and was sufficient to inhibit expression of the -5.3-kb Foxf1 promoter. Furthermore, C/EBPβ and HNF-6 proteins bound to the 3′RE region (+4647/+4694 bp) and provided synergistic transcriptional activation of the -5.3-kb Foxf1 promoter in cotransfection assays. These studies demonstrated that the conserved Foxf1 3′RE region is essential for proper tissue-specific regulation of the Foxf1 promoter region during mouse embryogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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18. Functional significance of protein kinase A activation by endothelin-1 and ATP: negative regulation of SRF-dependent gene expression by PKA
- Author
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Davis, Amanda, Hogarth, Kyle, Fernandes, Darren, Solway, Julian, Niu, Jiaxin, Kolenko, Vladimir, Browning, Darren, Miano, Joseph M., Orlov, Sergei N., and Dulin, Nickolai O.
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ENDOTHELINS , *SMOOTH muscle - Abstract
Endothelin-1 (ET1) and ATP stimulate contraction and hypertrophy of vascular smooth muscle cells (VSMC) by activating diverse signalling pathways. In this study, we show that in VSMC, ET1 and ATP stimulate transient and sustained activation of protein kinase A (PKA), respectively. Using a dominant negative PKA mutant (PKA-DN), we examined the functional significance of PKA activation in the signalling of ET1 and ATP. Overexpression of PKA-DN did not alter the ET1- or ATP-induced phosphorylation of the extracellular signal-regulated protein kinase, Erk2. ATP stimulated a profound, PKA-dependent activation of cAMP-response element (CRE), whereas the effect of ET1 was negligible. Both ET1 and ATP stimulated serum response factor (SRF)-dependent gene expression. Overexpression of PKA-DN potentiated the effects of ET1 and ATP on SRF activity, whereas stimulation of PKA by isoproterenol, forskolin or by overexpression of the PKA catalytic subunit decreased SRF activity. These data demonstrate that (i) PKA negatively regulates SRF activity and (ii) ET1 and ATP stimulate opposing pathways, whose balance determines the net activity of SRF. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
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