Abstract
ABSTRACTProstaglandin (PG)-E2 is essential for growth and development of vertebrates. PGE2 binds to G-coupled receptors to regulate embryonic stem cell differentiation and maintains tissue homeostasis. Overproduction of PGE2 by breast tumor cells promotes aggressive breast cancer phenotypes and tumor-associated lymphangiogenesis. In this study, we investigated novel roles of PGE2 in early embryonic vascular development and maturation with the microinjection of PGE2 in fertilized zebrafish (Danio rerio) eggs. We injected Texas Red dextran to trace vascular development. Embryos injected with the solvent of PGE2 served as vehicle. Distinct developmental changes were noted from 28–96 h post fertilization (hpf), showing an increase in embryonic tail flicks, pigmentation, growth, hatching and larval movement post-hatching in the PGE2-injected group compared to the vehicle. We recorded a significant increase in trunk vascular fluorescence and maturation of vascular anatomy, embryo heartbeat and blood vessel formation in the PGE2 injected group. At 96 hpf, all larvae were euthanized to measure vascular marker mRNA expression. We observed a significant increase in the expression of stem cell markers efnb2a, ephb4a, angiogenesis markers vegfa, kdrl, etv2 and lymphangiogenesis marker prox1 in the PGE2-group compared to the vehicle. This study shows the novel roles of PGE2 in promoting embryonic vascular maturation and angiogenesis in zebrafish.This article has an associated First Person interview with the first author of the paper.
Highlights
Prostaglandin (PG) E-2 is a prostanoid, which is endogenously synthesized from the arachidonic acid of vertebrate cell membranes by an enzyme, cyclooxygenase (COX)-2
Using rat lymphatic mesenteric lymphatic endothelial cells (RMLEC)s we showed that Prostaglandin E2 (PGE2) induced lymphangiogenesis in vitro could be abrogated with COX-2 inhibitor (COX2-I) and EP4 antagonist (EP4A) (Nandi et al, 2017)
It has been established that hematopoietic stem cells (HSC) homeostasis is tightly controlled by PGE2
Summary
Prostaglandin (PG) E-2 is a prostanoid, which is endogenously synthesized from the arachidonic acid of vertebrate cell membranes by an enzyme, cyclooxygenase (COX)-2. The role of PGE synthase (Ptges) in embryonic differentiation and growth in zebrafish was well investigated by Cha et al (2006). They showed that knockdown of Ptges in the zebrafish embryo completely abrogated early cell differentiation and cell polarization, which was retrieved with PGE2 addition, as embryos could recover all phenotypes. They have shown that PGE2 regulates zebrafish growth via EP4/PI3K/Akt pathways (Cha et al, 2006). This study showed that treatment with chemicals that enhance PGE2 synthesis induced HSC and in contrast, chemicals, which block prostaglandin synthesis, decreased stem cell numbers (North et al, 2007)
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