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Epigenetic Modifications in T Cells: The Role of DNA Methylation in Salt-Sensitive Hypertension.
Dasinger, John Henry; Alsheikh, Ammar J; Abais-Battad, Justine M; Pan, Xiaoqing; Fehrenbach, Daniel J; Lund, Hayley; Roberts, Michelle L; Cowley, Allen W; Kidambi, Srividya; Kotchen, Theodore A; Liu, Pengyuan; Liang, Mingyu; Mattson, David L.
Afiliación
  • Dasinger JH; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Alsheikh AJ; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Abais-Battad JM; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Pan X; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Fehrenbach DJ; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Lund H; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Roberts ML; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Cowley AW; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Kidambi S; Medicine (S.K., T.A.K.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Kotchen TA; Medicine (S.K., T.A.K.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Liu P; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Liang M; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
  • Mattson DL; From the Departments of Physiology (J.H.D., A.J.A., J.M.A.-B., X.P., D.J.F., H.L., M.L.R., A.W.C., P.L., M.L., D.L.M.), Medical College of Wisconsin Milwaukee, Wisconsin, USA.
Hypertension ; 75(2): 372-382, 2020 02.
Article en En | MEDLINE | ID: mdl-31838911
ABSTRACT
The SS (Dahl salt sensitive) rat is an established model of hypertension and renal damage that is accompanied with immune system activation in response to a high-salt diet. Investigations into the effects of sodium-independent and dependent components of the diet were shown to affect the disease phenotype with SS/MCW (JrHsdMcwi) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to grain-fed SS/CRL (JrHsdMcwiCrl) rats. Since contributions of the immune system, environment, and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these colonies. T cells isolated from kidneys of the 2 colonies revealed that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. In response to high-salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit a significant increase in differentially methylated regions with a preference for hypermethylation compared with the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between colonies. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. This study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Presión Sanguínea / Linfocitos T / Cloruro de Sodio Dietético / Metilación de ADN / Epigénesis Genética / Hipertensión Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: Hypertension Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Presión Sanguínea / Linfocitos T / Cloruro de Sodio Dietético / Metilación de ADN / Epigénesis Genética / Hipertensión Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: Hypertension Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos