Dysregulation of gene expression in ABCC6 knockdown HepG2 cells

• Autorzy: Miglionico R. , Armentano M. F. , Carmosino M. , Salvia A. M. , Cuviello F. , Bisaccia F. , Ostuni A.
• Języki publikacji: EN

Abstrakty

EN

ABCC6 protein is an ATP-dependent transporter that is mainly found in the basolateral plasma membrane of hepatocytes. ABCC6 deficiency is the primary cause of several forms of ectopic mineralization syndrome. Mutations in the human ABCC6 gene cause pseudoxanthoma elasticum (PXE), an autosomal recessive disease characterized by ectopic calcification of the elastic fibers in dermal, ocular and vascular tissues. Mutations in the mouse ABCC6 gene were also associated with dystrophic cardiac calcification. Reduced levels of ABCC6 protein were found in a β-thalassemic mouse model. Moreover, some cases of generalized arterial calcification in infancy are due to ABCC6 mutations. In order to study the role of ABCC6 in the pathogenesis of ectopic mineralization, the expressions of genes involved in this process were evaluated in HepG2 cells upon stable knockdown of ABCC6 by small hairpin RNA (shRNA) technology. ABCC6 knockdown in HepG2 cells causes a significant upregulation of the genes promoting mineralization, such as TNAP, and a parallel downregulation of genes with anti-mineralization activity, such as NT5E, Fetuin A and Osteopontin. Although the absence of ABCC6 has been already associated with ectopic mineralization syndromes, this study is the first to show a direct relationship between reduced ABCC6 levels and the expression of pro-mineralization genes in hepatocytes.

Słowa kluczowe

EN

dysregulation; gene expression; HepG2 cell; protein; plasma membrane; hepatocyte; ABCC6 gene; mutation

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2014
• Tom: 19
• Numer: 4
• Opis fizyczny: p.517-526,fig.,ref.

Twórcy

autor

Miglionico R.

• Department of Sciences, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100, Potenza, Italy

autor

Armentano M. F.

• Department of Sciences, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100, Potenza, Italy

autor

Carmosino M.

• Department of Sciences, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100, Potenza, Italy

autor

Salvia A. M.

• Department of Sciences, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100, Potenza, Italy

autor

Cuviello F.

• Department of Sciences, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100, Potenza, Italy

autor

Bisaccia F.

• Department of Sciences, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100, Potenza, Italy

autor

Ostuni A.

• Department of Sciences, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100, Potenza, Italy

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Identyfikatory

DOI

10.2478/s11658-014-0208-2