Gene Silencing of SOCS3 by siRNA Intranasal Delivery Inhibits Asthma Phenotype in Mice
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{"title"=>"Gene silencing of SOCS3 by siRNA intranasal delivery inhibits asthma phenotype in mice", "type"=>"journal", "authors"=>[{"first_name"=>"Ma Paz", "last_name"=>"Zafra", "scopus_author_id"=>"37098297400"}, {"first_name"=>"Carla", "last_name"=>"Mazzeo", "scopus_author_id"=>"35074587000"}, {"first_name"=>"Cristina", "last_name"=>"Gámez", "scopus_author_id"=>"57196998549"}, {"first_name"=>"Ainara Rodriguez", "last_name"=>"Marco", "scopus_author_id"=>"56881742900"}, {"first_name"=>"Ana", "last_name"=>"De Zulueta", "scopus_author_id"=>"56115383900"}, {"first_name"=>"Veronica", "last_name"=>"Sanz", "scopus_author_id"=>"55552164000"}, {"first_name"=>"Izaskun", "last_name"=>"Bilbao", "scopus_author_id"=>"24402931700"}, {"first_name"=>"Jesús", "last_name"=>"Ruiz-Cabello", "scopus_author_id"=>"7003625720"}, {"first_name"=>"Jose M.", "last_name"=>"Zubeldia", "scopus_author_id"=>"6503871740"}, {"first_name"=>"Victoria", "last_name"=>"Del Pozo", "scopus_author_id"=>"7003488867"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84898669702", "pui"=>"372838413", "doi"=>"10.1371/journal.pone.0091996", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84898669702", "pmid"=>"24637581"}, "id"=>"ebb14fee-6cf7-39db-93dc-e637a36563fc", "abstract"=>"Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma.", "link"=>"http://www.mendeley.com/research/gene-silencing-socs3-sirna-intranasal-delivery-inhibits-asthma-phenotype-mice", "reader_count"=>29, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>6, "Other"=>2, "Student > Master"=>4, "Student > Bachelor"=>2, "Professor"=>1, "Student > Postgraduate"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>6, "Other"=>2, "Student > Master"=>4, "Student > Bachelor"=>2, "Professor"=>1, "Student > Postgraduate"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>4, "Materials Science"=>2, "Medicine and Dentistry"=>5, "Agricultural and Biological Sciences"=>12, "Immunology and Microbiology"=>1, "Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>4}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1423693"], "description"=>"<p><b>A</b>. Airway hyperresponsiveness to methacholine challenge. Methacholine dose response curve 24 hours after last OVA administration. Saline group (mean ±SD, n = 13); OVA group (mean ±SD, n = 12); OVA siNT-treated group (mean ±SD, n = 12); and OVA siSOCS3-treated group (mean ±SD, n = 15). <b>B</b>. Native axial micro-CT images of the lungs of typical mice from each experimental group, where hyperintense areas (arrow) correspond to tissue with more fluid than normal. 1: SS n = 4; 2: OVA n = 4; 3: OVA siNT n = 4; 4: OVA siSOCS3 n = 4. *<i>P</i><0,05 between groups. <b>C</b>. In vivo FMT tomographic imaging. Lung fluorescence after ProSense 680 administration in mice. Three-dimensional regions of interest were placed within the lung region. 1: SS group; 2: OVA group; 3: OVA siNT group; 4: OVA siSOCS3 group. <b>C</b>. 3D FMT quantification of pulmonary inflammation, expressed as total pmoles per lung ± S.D (†<i>P</i><0,01) of ProSense 680 fluorescence within the lung region of each mouse from all the study groups (SS n = 4, OVA n = 4, OVA siNT n = 4, OVA siSOCS3 n = 4).</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "techniques", "socs3"], "article_id"=>964680, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091996.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vivo_techniques_to_assess_the_effect_of_SOCS3_gene_silencing_in_lungs_/964680", "title"=>"<i>In vivo</i> techniques to assess the effect of SOCS3 gene silencing in lungs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 03:53:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1423712", "https://ndownloader.figshare.com/files/1423713", "https://ndownloader.figshare.com/files/1423715", "https://ndownloader.figshare.com/files/1423716"], "description"=>"<div><p>Suppresors of cytokine signaling (SOCS) proteins regulate cytokine responses and control immune balance. Several studies have confirmed that SOCS3 is increased in asthmatic patients, and SOCS3 expression is correlated with disease severity. The objective of this study was to evaluate if delivering of SOCS3 short interfering RNA (siRNA) intranasally in lungs could be a good therapeutic approach in an asthma chronic mouse model. Our results showed that intranasal treatment with SOCS3-siRNA led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion, a reduction in lung collagen, which are prominent features of airway remodeling. The mechanism implies JAK/STAT and RhoA/Rho-kinase signaling pathway, because we found a decreasing in STAT3 phosphorylation status and down regulation of RhoA/Rho-kinase protein expression. These results might lead to a new therapy for the treatment of chronic asthma.</p></div>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "socs3", "sirna", "intranasal", "inhibits", "phenotype"], "article_id"=>964693, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0091996.s001", "https://dx.doi.org/10.1371/journal.pone.0091996.s002", "https://dx.doi.org/10.1371/journal.pone.0091996.s003", "https://dx.doi.org/10.1371/journal.pone.0091996.s004"], "stats"=>{"downloads"=>7, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_Silencing_of_SOCS3_by_siRNA_Intranasal_Delivery_Inhibits_Asthma_Phenotype_in_Mice_/964693", "title"=>"Gene Silencing of SOCS3 by siRNA Intranasal Delivery Inhibits Asthma Phenotype in Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-03-17 03:53:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1423690"], "description"=>"<p><b>A</b>. Red-labeled siRNA localization in mouse lung after intranasal delivery determined by confocal microscopy. 2 μM of siRNA was administered. 1: control mouse lung after 48 h after administration of distilled water. 2 and 4: Lung airway images after 24 h from siRNA delivery. 3 and 5: Lung airways 48 h after siRNA administration. <b>B</b>. Relative SOCS3 mRNA levels were determined by real-time quantitative PCR. The results show relative gene expressions as determined by the ΔΔC<sub>T</sub> method. <b>C</b>. SOCS3 Western blot analysis from lungs was achieved using an antibody against SOCS3 and β-actin. Lane 1: lung lysate from the SS group; lane 2: lung lysate from the OVA group; Lane 3: lung lysate from the OVA+siNT group; and lane 4: lung lysate from the OVA+siSOCS3 group. β-actin was used as a loading control. The picture is a representative example of several mice, all displaying similar results. <b>D</b>. SOCS3 bands were quantified by densitometry. SS group (mean ±SD, n = 13); OVA group (mean ±SD, n = 12); OVA siNT-treated group (mean ±SD, n = 12); OVA siSOCS3-treated group (mean ±SD, n = 15). ‡<i>P</i><0.001 and *<i>P</i><0.05 between groups.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models"], "article_id"=>964678, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091996.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SOCS3_gene_silencing_in_lung_/964678", "title"=>"SOCS3 gene silencing in lung.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 03:53:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1423708"], "description"=>"<p>Total lung proteins from mice for all the study groups were isolated and Western blot analyses were performed to measure p-STAT3, RhoA, and ROCK-2 activation. pSTAT3 expression was measured against total STAT3 protein (A) and densitometric quantified (B). ROCK-2 and RhoA expression were detected and normalized against β-actin protein (C). Band densitometries were performed to quantified protein of ROCK-2 (D) and RhoA (E). SS group (mean ±SD, n = 13); OVA group (mean ±SD, n = 12); OVA siNT-treated group (mean ±SD, n = 12); and OVA siSOCS3-treated group (mean ±SD, n = 15). †<i>P</i><0.01 between groups and *<i>P</i><0.05 between groups.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "routes", "modified", "socs3-sirna"], "article_id"=>964689, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091996.g006", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Signaling_routes_modified_after_SOCS3_siRNA_therapy_/964689", "title"=>"Signaling routes modified after SOCS3-siRNA therapy.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 03:53:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1423702"], "description"=>"<p>mRNA levels of IL-5 (A), IL-4 (B), IL-13 (C), INFγ (D), IL-10 (E), and IL-17A in lungs of different groups of mice, measured by real-time quantitative PCR. The results show relative gene expression as determined by the ΔΔC<sub>t</sub> method. SS group (mean ±SD, n = 13); OVA group (mean ±SD, n = 12); OVA siNT- treated group (mean ±SD, n = 12); and OVA siSOCS3-treated group (mean ±SD, n = 15). Significant differences for IL-5 and IL-4 (P<0.05) expression levels were obtained for OVA SOCS3-siRNA vs OVA and OVA siNT groups. For IL-13, IL-10, and IL-17A, significant differences were achieved only between the OVA and OVA SOCS3-siRNA groups (*<i>P</i><0.05 between groups).</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "socs3-sirna", "quantitative", "cytokine", "genes"], "article_id"=>964688, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091996.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_SOCS3_siRNA_therapy_on_quantitative_expression_of_cytokine_genes_in_lungs_/964688", "title"=>"Effect of SOCS3-siRNA therapy on quantitative expression of cytokine genes in lungs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 03:53:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1423699"], "description"=>"<p>Comparison of structural changes in airways of negative control (SS, n = 13), untreated positive control (OVA, n = 12), non-target siRNA-treated (siNT, n = 12), and SOCS3 siRNA-treated (SOCS3-siRNA, n = 15) mice shown with H&E (row A–D), PAS (row F–I) and Masson Trichrome (row J–M) staining of lung sections, in at least 3 independent experiments. Representative photomicrographs of excised pulmonary tissue from the saline group are in the first column, the second column presents the OVA group, the third depicts the OVA group, and the SOCS3- siRNA group is represented in the fourth column. <b>E</b>. Cell infiltration in the specimens. Saline group (mean ±SD, n = 13); OVA group (mean ±SD, n = 12); OVA siNT-treated group (mean ±SD, n = 12); and OVA siSOCS3-treated group (mean ±SD, n = 15). *<i>P</i><0.05 between groups.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "histopathologic", "findings", "socs3-sirna"], "article_id"=>964686, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091996.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pulmonary_histopathologic_findings_in_chronic_asthma_effect_of_SOCS3_siRNA_therapy_/964686", "title"=>"Pulmonary histopathologic findings in chronic asthma: effect of SOCS3-siRNA therapy.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 03:53:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1423695"], "description"=>"<p><b>A</b>. Total cell counts in BAL. <b>B</b>. Leukocyte population analysis by flow cytometry in BAL. SS group (mean ±SD, n = 13); OVA group (mean ±SD, n = 12); OVA siNT-treated group (mean ±SD, n = 12); and OVA siSOCS3-treated group (mean ±SD, n = 15) ‡<i>P</i><0.001 and *<i>P</i><0.05 between groups.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "populations"], "article_id"=>964682, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091996.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_cell_populations_in_BAL_/964682", "title"=>"Analysis of cell populations in BAL.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-17 03:53:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1423710"], "description"=>"<p>*Ig levels values represented (mean ± SD) for each group (12–17 mice/group).</p>†<p><i>P</i><0.05 vs other groups.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "ig"], "article_id"=>964691, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091996.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Total_and_specific_Ig_in_serum_/964691", "title"=>"Total and specific Ig in serum.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-17 03:53:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1423709"], "description"=>"<p>*miRNAs downregulated in the siRNA SOCS3-treated group.</p>†<p>miRNAs upregulated in the siRNA SOCS3-treated group.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "developmental biology", "Molecular development", "cytokines", "immunology", "Clinical immunology", "allergies", "molecular biology", "Molecular biology techniques", "Gene therapy", "physiology", "Immune physiology", "Pulmonology", "asthma", "Animal models of disease", "Model organisms", "Animal models", "Mouse models", "modulated", "mirnas", "socs3", "sirna", "compared", "non-treated", "asthmatic", "groups", "respective", "induction"], "article_id"=>964690, "categories"=>["Biological Sciences"], "users"=>["Carla Mazzeo", "Cristina Gámez", "Ainara Rodriguez Marco", "Ana de Zulueta", "Veronica Sanz", "Izaskun Bilbao", "Jesús Ruiz-Cabello", "Jose M. Zubeldia", "Victoria del Pozo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0091996.t002", "stats"=>{"downloads"=>5, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_List_of_significantly_modulated_miRNAs_after_SOCS3_siRNA_therapy_compared_to_the_non_treated_asthmatic_groups_P_/964690", "title"=>"List of significantly modulated miRNAs after SOCS3 siRNA therapy compared to the non-treated asthmatic groups (<i>P</i><0.05), and their respective fold induction (FI).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-17 03:53:32"}

PMC Usage Stats | Further Information

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