La transcriptómica del fracaso renal agudo revela una relación entre inflamación y envejecimiento

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Concepción Izquierdo, María Concepción Izquierdo, Ana B. Sanz, M. Dolores Sánchez-Niño, María Dolores Sánchez-Niño, M. Vanessa Pérez-Gómez, María Vanessa Perez-Gomez, Marta Ruiz-Ortega, Jonay Poveda, Olga Ruiz-Andrés, Olga Ruiz-Andres, Adrián M. Ramos, Juan A. Moreno, Jesús Egido, Alberto Ortiz" "autores" => array:19 [ 0 => array:2 [ "nombre" => "M. Concepción" "apellidos" => "Izquierdo" ] 1 => array:2 [ "nombre" => "María Concepción" "apellidos" => "Izquierdo" ] 2 => array:2 [ "nombre" => "Ana B." "apellidos" => "Sanz" ] 3 => array:2 [ "nombre" => "Ana B." "apellidos" => "Sanz" ] 4 => array:2 [ "nombre" => "M. Dolores" "apellidos" => "Sánchez-Niño" ] 5 => array:2 [ "nombre" => "María Dolores" "apellidos" => "Sánchez-Niño" ] 6 => array:2 [ "nombre" => "M. 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"apellidos" => "Moreno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "afff" ] ] ] 15 => array:3 [ "nombre" => "Jesús" "apellidos" => "Egido" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "affe" ] ] ] 16 => array:3 [ "nombre" => "Jesús" "apellidos" => "Egido" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "afff" ] ] ] 17 => array:4 [ "nombre" => "Alberto" "apellidos" => "Ortiz" "email" => array:1 [ 0 => "aortiz@fjd.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "affe" ] ] ] 18 => array:4 [ "nombre" => "Alberto" "apellidos" => "Ortiz" "email" => array:1 [ 0 => "aortiz@fjd.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "afff" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => " IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid and Fundación Renal Iñigo Álvarez de Toledo, Madrid, " "etiqueta" => "a" "identificador" => "affa" ] 1 => array:3 [ "entidad" => " IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid and Fundación Renal Iñigo Álvarez de Toledo, Madrid, Spain, " "etiqueta" => "b" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Servicio de Nefrología, IdiPAZ, Madrid, " "etiqueta" => "c" "identificador" => "affc" ] 3 => array:3 [ "entidad" => "Servicio de Nefrología, IdiPAZ, Madrid, Spain, " "etiqueta" => "d" "identificador" => "affd" ] 4 => array:3 [ "entidad" => " IIS-Fundación Jiménez Díaz. Universidad Autónoma, Madrid, " "etiqueta" => "e" "identificador" => "affe" ] 5 => array:3 [ "entidad" => " IIS-Fundación Jiménez Díaz. Universidad Autónoma, Madrid, Spain, " "etiqueta" => "f" "identificador" => "afff" ] ] ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Acute kidney injury transcriptomics unveils a relationship between inflammation and ageing" ] ] "pdfFichero" => "P1-E544-S3765-A11667.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:6 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec431637" "palabras" => array:1 [ 0 => "Enfermedad renal crónica" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec431639" "palabras" => array:1 [ 0 => "Envejecimiento" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec431641" "palabras" => array:1 [ 0 => "Fracaso renal agudo" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec431643" "palabras" => array:1 [ 0 => "Klotho" ] ] 4 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec431645" "palabras" => array:1 [ 0 => "TWEAK" ] ] 5 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec431647" "palabras" => array:1 [ 0 => "Inflamación" ] ] ] "en" => array:6 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec431638" "palabras" => array:1 [ 0 => "Chronic kidney disease" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec431640" "palabras" => array:1 [ 0 => "Aging" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec431642" "palabras" => array:1 [ 0 => "Acute kidney injury" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec431644" "palabras" => array:1 [ 0 => "Klotho" ] ] 4 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec431646" "palabras" => array:1 [ 0 => "TWEAK" ] ] 5 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec431648" "palabras" => array:1 [ 0 => "Inflammation" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "No existen estrategias terapéuticas y fisiopatológicas para el fracaso renal agudo (FRA), por lo que los niveles de mortalidad continúan siendo elevados. Además, la enfermedad renal crónica (ERC) predispone a sufrir FRA y el FRA, a su vez, contribuye a que la ERC avance. Recientemente, una estrategia transcriptómica reveló una relación entre el FRA, la inflamación y la regulación del envejecimiento. Un análisis transcriptómico de modelos experimentales de FRA reveló un aumento de la expresión renal de Fn14 y la quimiocina transmembrana CXCL16, así como un descenso en la expresión de la hormona Klotho antienvejecimiento secretada por el riñón. Fn14 es el receptor de la citoquina tumor necrosis factor-like weak inducer of apoptosis (TWEAK), miembro de la superfamilia de factor de necrosis tumoral. En los riñones con FRA, existía una correlación positiva entre Fn14 y la expresión de ARNm de CXCL16 y una correlación inversa entre Fn14 y el ARNm de Klotho. El lugar donde se da la expresión in vivo de Fn14, CXCL16 y Klotho es las células tubulares. La investigación en las relaciones entre estas tres moléculas reveló que la activación de Fn14 por TWEAK provocó la inflamación mediante la secreción de quimiocinas como la CXCL16 en células tubulares, tanto en cultivo como in vivo. Además, la activación de Fn14 por TWEAK disminuyó la expresión de ARNm de Klotho y de proteína, en cultivo y in vivo. Curiosamente, tanto la activación TWEAK de la trascripción de ARNm de CXCL16 y la supresión de la trascripción de ARNm de Klotho estuvieron mediadas por el factor de transcripción NF-kB. Como conclusión, la unión de TWEAK y Fn14 es un elemento clave en promover de la activación mediada por NF-kB de las vías de inflamación y en la supresión de las vías antiinflamatorias y antienvejecimiento. Esta información puede influir en las futuras estrategias terapéuticas para el FRA y la inflamación/envejecimiento." ] "en" => array:1 [ "resumen" => "There are no pathophysiolgical therapeutic approaches to acute kidney injury (AKI) and the mortality remains high. In addition chronic kidney disease (CKD) predisposes to AKI and AKI contributes to progression of CKD. Recently a transcriptomics approach unveiled a relationship between AKI, inflammation and the regulation of ageing. A transcriptomics analysis of experimental AKI revealed increased kidney expression of Fn14 and transmembrane chemokine CXCL16, as well as a decreased expression of the kidney-secreted anti-ageing hormone Klotho. Fn14 is the receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily. In AKI kidneys there was a positive correlation between Fn14 and CXCL16 mRNA expression and an inverse correlation between Fn14 and Klotho mRNA. Tubular cells were the site of Fn14, CXCL16 and Klotho expression in vivo. Research on the relationships between these three molecules disclosed that TWEAK activation of Fn14 promoted inflammation through secretion of chemokines such as CXL16 in tubular cells in culture and in vivo. Furthermore, TWEAK activation of Fn14 decreased expression of Klotho mRNA and protein in culture and in vivo. Interestingly, both TWEAK activation of CXCL16 mRNA transcription and suppression of Klotho mRNA transcription were mediated by the NFκB transcription factor. In conclusion, TWEAK engagement of Fn14 is a central event promoting NFκB-mediated activation of inflammation pathways and suppression of anti-inflammatory/anti-ageing pathways. 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Acute kidney injury transcriptomics unveils a relationship between inflammation and ageing

M. Concepción Izquierdoa, María Concepción Izquierdob, Ana B. Sanzc, Ana B. Sanzd, M. Dolores Sánchez-Niñoc, María Dolores Sánchez-Niñod, M. Vanessa Pérez-Gómeza, María Vanessa Perez-Gomezb, Marta Ruiz-Ortegab, Jonay Povedae, Jonay Povedaf, Olga Ruiz-Andrése, Olga Ruiz-Andresf, Adrián M. Ramosf, Juan A. Morenof, Jesús Egidoe, Jesús Egidof, Alberto Ortize, Alberto Ortizf

a IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid and Fundación Renal Iñigo Álvarez de Toledo, Madrid,

b IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid and Fundación Renal Iñigo Álvarez de Toledo, Madrid, Spain,

c Servicio de Nefrología, IdiPAZ, Madrid,

d Servicio de Nefrología, IdiPAZ, Madrid, Spain,

e IIS-Fundación Jiménez Díaz. Universidad Autónoma, Madrid,

f IIS-Fundación Jiménez Díaz. Universidad Autónoma, Madrid, Spain,

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        "resumen" => "<p class="elsevierStylePara">No existen estrategias terap&#233;uticas y fisiopatol&#243;gicas para el fracaso renal agudo &#40;FRA&#41;&#44; por lo que los niveles de mortalidad contin&#250;an siendo elevados&#46; Adem&#225;s&#44; la enfermedad renal cr&#243;nica &#40;ERC&#41; predispone a sufrir FRA y el FRA&#44; a su vez&#44; contribuye a que la ERC avance&#46; Recientemente&#44; una estrategia transcript&#243;mica revel&#243; una relaci&#243;n entre el FRA&#44; la inflamaci&#243;n y la regulaci&#243;n del envejecimiento&#46; Un an&#225;lisis transcript&#243;mico de modelos experimentales de FRA revel&#243; un aumento de la expresi&#243;n renal de Fn14 y la quimiocina transmembrana CXCL16&#44; as&#237; como un descenso en la expresi&#243;n de la hormona Klotho antienvejecimiento secretada por el ri&#241;&#243;n&#46; Fn14 es el receptor de la citoquina tumor necrosis factor-like weak inducer of apoptosis &#40;TWEAK&#41;&#44; miembro de la superfamilia de factor de necrosis tumoral&#46; En los ri&#241;ones con FRA&#44; exist&#237;a una correlaci&#243;n positiva entre Fn14 y la expresi&#243;n de ARNm de CXCL16 y una correlaci&#243;n inversa entre Fn14 y el ARNm de Klotho&#46; El lugar donde se da la expresi&#243;n in vivo de Fn14&#44; CXCL16 y Klotho es las c&#233;lulas tubulares&#46; La investigaci&#243;n en las relaciones entre estas tres mol&#233;culas revel&#243; que la activaci&#243;n de Fn14 por TWEAK provoc&#243; la inflamaci&#243;n mediante la secreci&#243;n de quimiocinas como la CXCL16 en c&#233;lulas tubulares&#44; tanto en cultivo como in vivo&#46; Adem&#225;s&#44; la activaci&#243;n de Fn14 por TWEAK disminuy&#243; la expresi&#243;n de ARNm de Klotho y de prote&#237;na&#44; en cultivo y in vivo&#46; Curiosamente&#44; tanto la activaci&#243;n TWEAK de la trascripci&#243;n de ARNm de CXCL16 y la supresi&#243;n de la trascripci&#243;n de ARNm de Klotho estuvieron mediadas por el factor de transcripci&#243;n NF-kB&#46; Como conclusi&#243;n&#44; la uni&#243;n de TWEAK y Fn14 es un elemento clave en promover de la activaci&#243;n mediada por NF-kB de las v&#237;as de inflamaci&#243;n y en la supresi&#243;n de las v&#237;as antiinflamatorias y antienvejecimiento&#46; Esta informaci&#243;n puede influir en las futuras estrategias terap&#233;uticas para el FRA y la inflamaci&#243;n&#47;envejecimiento&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara">There are no pathophysiolgical therapeutic approaches to acute kidney injury &#40;AKI&#41; and the mortality remains high&#46; In addition chronic kidney disease &#40;CKD&#41; predisposes to AKI and AKI contributes to progression of CKD&#46; Recently a transcriptomics approach unveiled a relationship between AKI&#44; inflammation and the regulation of ageing&#46; A transcriptomics analysis of experimental AKI revealed increased kidney expression of Fn14 and transmembrane chemokine CXCL16&#44; as well as a decreased expression of the kidney-secreted anti-ageing hormone Klotho&#46; Fn14 is the receptor for tumor necrosis factor-like weak inducer of apoptosis &#40;TWEAK&#41;&#44; a member of the TNF superfamily&#46; In AKI kidneys there was a positive correlation between Fn14 and CXCL16 mRNA expression and an inverse correlation between Fn14 and Klotho mRNA&#46; Tubular cells were the site of Fn14&#44; CXCL16 and Klotho expression in vivo&#46; Research on the relationships between these three molecules disclosed that TWEAK activation of Fn14 promoted inflammation through secretion of chemokines such as CXL16 in tubular cells in culture and in vivo&#46; Furthermore&#44; TWEAK activation of Fn14 decreased expression of Klotho mRNA and protein in culture and in vivo&#46; Interestingly&#44; both TWEAK activation of CXCL16 mRNA transcription and suppression of Klotho mRNA transcription were mediated by the NF&#954;B transcription factor&#46; In conclusion&#44; TWEAK engagement of Fn14 is a central event promoting NF&#954;B-mediated activation of inflammation pathways and suppression of anti-inflammatory&#47;anti-ageing pathways&#46; This information may influence future therapeutic approaches to AKI and inflammation&#47;aging&#46;</p>"
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Información del artículo

ISSN: 02116995
Idioma original: Español

DOI:10.3265/Nefrologia.pre2012.Aug.11667

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