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Significant improvement of cardiac outflow tract septation defects in a DiGeorge syndrome model after minoxidil treatment.
Aurigemma, Ilaria; Ferrentino, Rosa; Krishnan, Varsha Poondi; Lanzetta, Olga; Angelini, Claudia; Illingworth, Elizabeth; Baldini, Antonio.
Afiliación
  • Aurigemma I; Dept of Chemistry and Biology, University of Salerno, Italy.
  • Ferrentino R; Institute of Genetics and Biophysics, CNR, Naples, Italy.
  • Krishnan VP; Institute of Genetics and Biophysics, CNR, Naples, Italy.
  • Lanzetta O; Institute of Genetics and Biophysics, CNR, Naples, Italy.
  • Angelini C; Istituto Applicazioni Del Calcolo CNR, Naples, Italy.
  • Illingworth E; Dept of Chemistry and Biology, University of Salerno, Italy.
  • Baldini A; Dept of Molecular Medicine and Medical Biotechnology, Univ. Federico II, Naples, Italy. Electronic address: antonio.baldini@unina.it.
Biochem Biophys Res Commun ; 720: 150104, 2024 Aug 06.
Article en En | MEDLINE | ID: mdl-38749189
ABSTRACT
The T-BOX transcription factor TBX1 is essential for the development of the pharyngeal apparatus and it is haploinsufficient in DiGeorge syndrome (DGS), a developmental anomaly associated with congenital heart disease and other abnormalities. The murine model recapitulates the heart phenotype and showed collagen accumulation. We first used a cellular model to study gene expression during cardiogenic differentiation of WT and Tbx1-/- mouse embryonic stem cells. Then we used a mouse model of DGS to test whether interfering with collagen accumulation using an inhibitor of lysyl hydroxylase would modify the cardiac phenotype of the mutant. We found that loss of Tbx1 in a precardiac differentiation model was associated with up regulation of a subset of ECM-related genes, including several collagen genes. In the in vivo model, early prenatal treatment with Minoxidil, a lysyl hydroxylase inhibitor, ameliorated the cardiac outflow tract septation phenotype in Tbx1 mutant fetuses, but it had no effect on septation in WT fetuses. We conclude that TBX1 suppresses a defined subset of ECM-related genes. This function is critical for OFT septation because the inhibition of collagen cross-linking in the mutant reduces significantly the penetrance of septation defects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Dominio T Box / Síndrome de DiGeorge / Modelos Animales de Enfermedad / Minoxidil Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Dominio T Box / Síndrome de DiGeorge / Modelos Animales de Enfermedad / Minoxidil Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos