P-2 NASH IS IMPROVED THROUGH MODIFICATIONS IN H3K9 METHYLATION BY PIRFENIDONE ACTING AS JMJD2B DEMETHYLASE ANTAGONIST.

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"tieneTextoCompleto" => 0 "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Samael Rodríguez, Rebeca Rosas, Angel Omar Vazquez, Ivonne Palacios, Ricardo De la Rosa, Rebeca Escutia, Josep Jiménez, Luis Felipe Jave, Arturo Santos, Ana Sandoval, Juan Armendariz" "autores" => array:11 [ 0 => array:3 [ "nombre" => "Samael" "apellidos" => "Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "aff0001" ] ] ] 1 => array:3 [ "nombre" => "Rebeca" "apellidos" => "Rosas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "aff0001" ] ] ] 2 => array:3 [ "nombre" => "Angel Omar" "apellidos" => "Vazquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "aff0001" ] ] ] 3 => array:3 [ "nombre" => "Ivonne" "apellidos" => "Palacios" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "2" "identificador" => "aff0002" ] ] ] 4 => array:3 [ "nombre" => "Ricardo De" "apellidos" => "la Rosa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "aff0001" ] ] ] 5 => array:3 [ "nombre" => "Rebeca" "apellidos" => "Escutia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "aff0001" ] ] ] 6 => array:3 [ "nombre" => "Josep" "apellidos" => "Jiménez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "2" "identificador" => "aff0002" ] ] ] 7 => array:3 [ "nombre" => "Luis Felipe" "apellidos" => "Jave" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "3" "identificador" => "aff0003" ] ] ] 8 => array:3 [ "nombre" => "Arturo" "apellidos" => "Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "4" "identificador" => "aff0004" ] ] ] 9 => array:3 [ "nombre" => "Ana" "apellidos" => "Sandoval" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "aff0001" ] ] ] 10 => array:3 [ "nombre" => "Juan" "apellidos" => "Armendariz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "1" "identificador" => "aff0001" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Biología Molecular y Genómica, Universidad de Guadalajara, Guadalajara, México" "etiqueta" => "1" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "Biochemistry and Physiology, Universitat de Barcelona, Barcelona, España" "etiqueta" => "2" "identificador" => "aff0002" ] 2 => array:3 [ "entidad" => "Inmunología, IMSS/CIBO, Guadalajara, México" "etiqueta" => "3" "identificador" => "aff0003" ] 3 => array:3 [ "entidad" => "EMCS, Tecnológico de Monterrey, Guadalajara, México" "etiqueta" => "4" "identificador" => "aff0004" ] ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "resumen" => "Introduction and ObjectivesNASH is characterized by hepatic lipid accumulation and inflammation and Jmjd2b up-regulation has been linked with this illness progression. Pirfenidone is an antifibrotic agent with anti-inflammatory and antioxidant effects recognized to decrease NASH features. Here, we report epigenetics mechanisms related to PFD-induced histone modifications involved in experimental NASH. This study aimed to investigate PFD as an epigenetic regulator in the Jmjd2b pathway by demethylating H3k9me3 in a NASH animal model. Material and MethodsMale C57BL/6J mice were fed with either normo-diet, or high fat/carbohydrate-containing diet (HF) for 16 weeks. A HF-subgroup was treated with PFD 300 mg/kg/d from week 8th to the end of protocol. Weight was recorded on weekly basis. Insulin tolerance test was performed at the end of treatment. Dual channel microarrays were hybridized to the Mus musculus genome version with 22,000 genes using hepatic mRNAs. Liver and fat histological analyses were carried out, and liver proteins were analyzed by western blot and Chromatin immunoprecipitation (ChIP). Molecular docking was used to validate binding of PFD to JMJD2BBBBB. ResultsCompared with HF group, mice treated with PFD reduced weight gain, hepatic fat accumulation, and epididymal fat. In addition, treatment drastically decreased cholesterol, triglycerides and VLDL, ALT and AST. Inflammatory nodules, fibrosis, and steatosis in liver tissue were also reduced. Besides, PFD modified expression of genes, such as, Jmjd2b, Pparg, Fasn and Srebp1. Likewise, PFD restored the repressive marks in H3k9, suggesting its capacity as an epigenetic regulator by decreasing Jmjd2b protein activity and interacting with its catalytic site (JmjC). ConclusionsPFD played an important role as an epigenetic regulator modifying Jmjd2b activity and improving NASH features." 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Samael Rodríguez1, Rebeca Rosas1, Angel Omar Vazquez1, Ivonne Palacios2, Ricardo De la Rosa1, Rebeca Escutia1, Josep Jiménez2, Luis Felipe Jave3, Arturo Santos4, Ana Sandoval1, Juan Armendariz1

1 Biología Molecular y Genómica, Universidad de Guadalajara, Guadalajara, México

2 Biochemistry and Physiology, Universitat de Barcelona, Barcelona, España

3 Inmunología, IMSS/CIBO, Guadalajara, México

4 EMCS, Tecnológico de Monterrey, Guadalajara, México

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        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0001">Introduction and Objectives</span><p id="spara001" class="elsevierStyleSimplePara elsevierViewall">NASH is characterized by hepatic lipid accumulation and inflammation and Jmjd2b up-regulation has been linked with this illness progression&#46; Pirfenidone is an antifibrotic agent with anti-inflammatory and antioxidant effects recognized to decrease NASH features&#46; Here&#44; we report epigenetics mechanisms related to PFD-induced histone modifications involved in experimental NASH&#46; This study aimed to investigate PFD as an epigenetic regulator in the Jmjd2b pathway by demethylating H3k9me3 in a NASH animal model&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Material and Methods</span><p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Male C57BL&#47;6J mice were fed with either normo-diet&#44; or high fat&#47;carbohydrate-containing diet &#40;HF&#41; for 16 weeks&#46; A HF-subgroup was treated with PFD 300 mg&#47;kg&#47;d from week 8th to the end of protocol&#46; Weight was recorded on weekly basis&#46; Insulin tolerance test was performed at the end of treatment&#46; Dual channel microarrays were hybridized to the Mus musculus genome version with 22&#44;000 genes using hepatic mRNAs&#46; Liver and fat histological analyses were carried out&#44; and liver proteins were analyzed by western blot and Chromatin immunoprecipitation &#40;ChIP&#41;&#46; Molecular docking was used to validate binding of PFD to JMJD2BBBBB&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Results</span><p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Compared with HF group&#44; mice treated with PFD reduced weight gain&#44; hepatic fat accumulation&#44; and epididymal fat&#46; In addition&#44; treatment drastically decreased cholesterol&#44; triglycerides and VLDL&#44; ALT and AST&#46; Inflammatory nodules&#44; fibrosis&#44; and steatosis in liver tissue were also reduced&#46; Besides&#44; PFD modified expression of genes&#44; such as&#44; Jmjd2b&#44; Pparg&#44; Fasn and Srebp1&#46; Likewise&#44; PFD restored the repressive marks in H3k9&#44; suggesting its capacity as an epigenetic regulator by decreasing Jmjd2b protein activity and interacting with its catalytic site &#40;JmjC&#41;&#46;</p></span> <span id="abss0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Conclusions</span><p id="spara005" class="elsevierStyleSimplePara elsevierViewall">PFD played an important role as an epigenetic regulator modifying Jmjd2b activity and improving NASH features&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abss0001"
            "titulo" => "Introduction and Objectives"
          ]
          1 => array:2 [
            "identificador" => "abss0002"
            "titulo" => "Material and Methods"
          ]
          2 => array:2 [
            "identificador" => "abss0004"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abss0005"
            "titulo" => "Conclusions"
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
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