MicroRNA regulation of the IGF axis
Fetal growth restriction is associated with abnormal placental cell (cytotrophoblast) proliferation. Using an explant model of human first trimester placenta, we have demonstrated that the IGF-I and -II stimulate proliferation in cytotrophoblast and are probably essential for normal placental growth. IGF activates signalling through IGF1R/Akt/ ERK pathways, thus the ability of the placenta to modulate expression of components of these pathways is important for normal pregnancy outcome. Endogenously, gene expression can be regulated by microRNAs (miRs); the human placenta contains high levels of these molecules thus we explored the possibility that miRs may be important for regulating IGF signalling and placental growth. Using an siRNA based approach to globally reduce miRs from the human placenta ex-vivo, we have established that miRs are important mediators of placental growth. Furthermore, by using a systems biology based approach, we have now identified novel miRs within the IGF axis in the placenta. The individual miRs within the IGF axis in the placenta will be described, and I will discuss how some miRs function to regulate expression of molecules within the IGF axis whilst others are themselves regulated by IGF. The IGF-axis is important for both the regulation of normal physiology, as well as a number of pathological states thus in addition to identifying a number of novel molecules that are important regulators of fetal growth, this work has implications for many other biological systems.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.