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Role of dipeptidyl peptidase-4 as a potentiator of activin/nodal signaling pathway
Dong-Seok Park1, Kyuhee Kim1, Minjoo Jang1, Sun-Cheol Choi1,*
1Department of Biomedical Sciences, University of Ulsan College of Medicine
Abstract
DPP4 (dipeptidyl peptidase—4), a highly conserved transmembrane glycoprotein with an exo-peptidase activity, has been shown to contribute to glucose metabolism, immune regulation, signal transduction, and cell differentiation. Here, we show that DPP4 is involved in control of activin/nodal signaling in Xenopus early development. In support of this, the gain of function of DPP4 augmented both Smad2 phosphorylation and the expression of target genes induced by activin or nodal signal. In addition, Dpp4 and Xnr1 showed a synergistic effect on the induction of ectopic dorsal body axis when co-injected at the suboptimal doses in early embryos. Conversely, saxagliptin, a DPP4 inhibitor repressed activin induction of Smad2 phosphorylation. Notably, overexpression of Dpp4 disrupted specification of dorsal body axis of embryo, leading to malformed phenotypes such as spina bifida and a shortened and dorsally bent axis. Taken together, these results suggest that DPP4 functions as a potentiator of activin/nodal signaling pathway.
Abstract, Accepted Manuscript(in press) [Submitted on September 12, 2018, Accepted on October 22, 2018]
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