Background: Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting the neurodevelopment, gastrointestinal, musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes. These genes codify for the “cohesin complex” playing a role in chromatid adhesion, DNA repair and gene expression regulation. The aim of this study was to investigate retinoic acid (RA) signaling pathway, a master developmental regulator, in CdLS cells. Methods: Skin biopsies from CdLS patients and healthy controls were cultured and derived primary fibroblast cells were treated with RA or dimethyl sulfoxide (vehicle). After RA treatment, cells were harvested and RNA was isolated for quantitative real-time polymerase chain reaction experiments. Results: We analyzed several components of RA metabolism in a human cell line of kidney fibroblasts (293T), in addition to fibroblasts collected from both NIPBL-mutated patients and healthy donors, with or without RA treatment. In all cases, ADH and RALDH1 gene expression was not affected by RA treatment, while CRABP1 was induced. CRABP2 was dramatically upregulated upon RA treatment in healthy donors but not in CdLS patients cells. Conclusion: We investigated if CdLS alterations are associated to perturbation of RA signaling. Cells derived from CdLS patients do not respond to RA signaling as efficiently as healthy controls. RA pathway alterations suggest a possible underlying mechanism for several cellular and developmental abnormalities associated with cohesin function. Birth Defects Research 109:1268–1276, 2017. © 2017 Wiley Periodicals, Inc.

Fazio, G., Bettini, L., Rigamonti, S., Meta, D., Biondi, A., Cazzaniga, G., et al. (2017). Impairment of Retinoic Acid Signaling in Cornelia de Lange Syndrome Fibroblasts. BIRTH DEFECTS RESEARCH, 109(16), 1268-1276 [10.1002/bdr2.1070].

Impairment of Retinoic Acid Signaling in Cornelia de Lange Syndrome Fibroblasts

Fazio, Grazia;Bettini, Laura Rachele;Biondi, Andrea;Cazzaniga, Giovanni;
2017

Abstract

Background: Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting the neurodevelopment, gastrointestinal, musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes. These genes codify for the “cohesin complex” playing a role in chromatid adhesion, DNA repair and gene expression regulation. The aim of this study was to investigate retinoic acid (RA) signaling pathway, a master developmental regulator, in CdLS cells. Methods: Skin biopsies from CdLS patients and healthy controls were cultured and derived primary fibroblast cells were treated with RA or dimethyl sulfoxide (vehicle). After RA treatment, cells were harvested and RNA was isolated for quantitative real-time polymerase chain reaction experiments. Results: We analyzed several components of RA metabolism in a human cell line of kidney fibroblasts (293T), in addition to fibroblasts collected from both NIPBL-mutated patients and healthy donors, with or without RA treatment. In all cases, ADH and RALDH1 gene expression was not affected by RA treatment, while CRABP1 was induced. CRABP2 was dramatically upregulated upon RA treatment in healthy donors but not in CdLS patients cells. Conclusion: We investigated if CdLS alterations are associated to perturbation of RA signaling. Cells derived from CdLS patients do not respond to RA signaling as efficiently as healthy controls. RA pathway alterations suggest a possible underlying mechanism for several cellular and developmental abnormalities associated with cohesin function. Birth Defects Research 109:1268–1276, 2017. © 2017 Wiley Periodicals, Inc.
Articolo in rivista - Articolo scientifico
Cornelia de Lange syndrome; fibroblasts; retinoic acid;
Cornelia de Lange syndrome; fibroblasts; retinoic acid; Aldehyde Dehydrogenase; Cell Cycle Proteins; Cell Line; Chromosomal Proteins, Non-Histone; De Lange Syndrome; Fibroblasts; Gene Expression; Genes, cdc; HEK293 Cells; Humans; Mutation; Neurophysins; Protein Precursors; Receptors, Retinoic Acid; Signal Transduction; Skin; Tretinoin; Vasopressins; Pediatrics, Perinatology and Child Health; Embryology; Toxicology; Developmental Biology; Health, Toxicology and Mutagenesis
English
1268
1276
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Fazio, G., Bettini, L., Rigamonti, S., Meta, D., Biondi, A., Cazzaniga, G., et al. (2017). Impairment of Retinoic Acid Signaling in Cornelia de Lange Syndrome Fibroblasts. BIRTH DEFECTS RESEARCH, 109(16), 1268-1276 [10.1002/bdr2.1070].
Fazio, G; Bettini, L; Rigamonti, S; Meta, D; Biondi, A; Cazzaniga, G; Selicorni, A; Massa, V
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/226318
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