New insights into the pathobiology of Down syndrome – hyaluronan synthase‐2 overexpression is regulated by collagen VI α2 chain. (28th March 2013)

• Record Type: Journal Article
• Authors: Karousou, Evgenia; Stachtea, Xanthi; Moretto, Paola; Viola, Manuela; Vigetti, Davide; D'Angelo, Maria Luisa; Raio, Luigi; Ghezzi, Fabio; Pallotti, Francesco; De, Giancarlo; Karamanos, Nikos K.; Passi, Alberto
• Is Part Of: FEBS journal. Volume 280:Number 10(2013)
• Page Start: 2418
• Page End: 2430
• Publication Date: 2013-03-28
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.12220
• Languages: English
• ISSNs: 1742-464X

Abstract

<abstract abstract-type="main" id="febs12220-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Down syndrome (DS) is a common birth defect characterized by the trisomy of chromosome 21. DS‐affected umbilical cords (UCs) of fetuses show altered architecture of the extracellular matrix. Overexpression of the chromosome 21 genes encoding the collagen type VI (COLVI) chains α1(VI) and α2(VI), <italic>COL6A1</italic> and <italic>COL6A2</italic>, respectively, has also reported to occur in the nuchal skin of DS fetuses. The aim of this study was therefore to evaluate the COLVI content in euploid and DS‐affected UCs and human skin fibroblasts, and to investigate the relationships between COLVI and hyaluronan (HA) and HA synthase‐2 (HAS2). We found that the UCs of DS fetuses showed denser staining of COLVI and increased <italic>COL6A2</italic> expression at both early and term gestational ages. <italic>In vitro</italic> expression studies in DS‐derived fibroblasts showed similarly increased amounts of α1(VI) and α2(VI) chains at the protein and transcriptional level, supporting the hypothesis of the gene dosage effect. Furthermore, increased levels of HA and <italic>HAS2</italic> were also found in DS‐derived skin fibroblast cultures. Notably, silencing of <italic>COL6A2</italic> in DS‐derived cells resulted in downregulation of <italic>HAS2</italic>, with a simultaneous decrease in secreted HA. Exogenous addition of COLVI to normal fibroblasts did not have any effect on <italic>HAS2</italic> expression. In conclusion, UCs and skin fibroblasts in DS show significant increases in COLVI and HA; the overexpression of <italic>COL6A2</italic> in DS tissue and cells is closely related to the increased expression of <italic>HAS2</italic>. These data may explain the DS phenotypes and their effects in organ tissue maturation.</p> </abstract>