Reciprocal Role of DKK1 and DKK2 in Vascular

Reciprocal Role of DKK1 and DKK2 in Vascular Development

Vijayendra Agrawal, Jeong-Ki Min and Young-Guen Kwon.

Department of Biochemistry, College of Natural Sciences, Yonsei University, Seoul, Korea

Abstract

The angiogenic process involves diverse cellular actions such as remodeling of extracellular matrix (ECM) and proliferation, migration, and morphogenetic differentiation of ECs. The current study was undertaken to scrutinize the genetic transformation during morphogenic differentiation in vitro and in vivo. DNA chip microarray analysis divulged the involvement of numerous genes, which were upregulated and/or downregulated with morphological transformation of ECs on two-dimensional Matrigel. Amongst hordes of altered genes, reciprocal expression of dickkopfs (DKK1 and DKK2; regulators of Wnt signalling pathway) was tracked during ECs morphogenesis. Down regulation of DKK1, whereas upregulation of DKK2 was substantiated during ECM recognition and morphological revolutionization of ECs. In vivo studies unveiled abeyant blood vessels development in DKK1 transgenic mouse embryos, while ameliorated vascular augmentation was affirmed in DKK2 transgenic mouse embryos. These affirmations insinuate that DKKs may serve as prime regulators of EC morphogenesis and vascular development.