Identification of a Novel Spliced Variant of ADAMTS13 in Human Mesenchymal Stem Cells

Abstract

ADAMTS13 is a matrix metalloproteinase that cleaves von Willebrand factor (vWF) into small multimers. Several truncated forms of ADAMTS13 can be detected in plasma, generated due to alternative splicing or proteolysis by serine proteases. In this study, for the first time, we report an alternatively spliced variant of ADAMTS13 that is expressed in human mesenchymal stem cells (MSCs), derived from both the Whartons Jelly (WJ) of umbilical cords and the decidua-basalis layer of the placenta (PL). Our results demonstrated that the variant contained the signal peptide (Sp), propeptide (P), metalloprotease (Mp), disintegrin-like (Dis), thrombospondin type-1 repeat 1 (Tsp1-1) and cysteine-rich (Cys) domains, while the spacer (Spc) and CUB domains were absent. The Tsp1-2-8 domain was partially present. Additionally, this variant possessed partial vWF cleavage activity compared to full-length ADAMTS13. Thus, we identified a novel isoform of ADAMTS13, generated due to exon skipping in human MSCs, which retained partial activity towards vWF cleavage.