Extracellular matrix-dependent regulation of angiogenin expression in human placenta

Knowledge of the rapidly developing hierarchy of controls affecting vascular development in placenta is required to understand how the growth factors and their receptor-mediated signals actually produce vessels. At the cell biological level, these events clearly require stable interactions between the cells, and cells with the surrounding ECM. The objective of the study was to understand the role of integrins and ECM on the expression and secretion of angiogenin in placentas and from trophoblasts in culture. Functionally active term placental explant culture and trophoblast cultures were used to demonstrate the differential secretion profile of angiogenin and real-time quantitative RT-PCR to demonstrate the mRNA expression in the presence or absence of ECM proteins. In this study, a significant increase in expression and secretion of angiogenin occurred in the presence of vitronectin (VN) and fibronectin (FN). Using antibody-blocking experiments it was also demonstrated that the angiogenin secretion is mediated by placental integrins, alpha(V)beta3 and alpha5beta1. In addition, exposure to hypoxic conditions resulted in diminished angiogenin secretion in the presence of both ECMs suggesting that angiogenin expression in the presence of ECM is modulated by local O2 concentration. In conclusion, this study provides evidence for the regulatory role of ECM and integrins on the mRNA expression and secretion of angiogenin in human placenta. ECMs may have a pivotal role in enhancing secretion of this peptide necessary for placental angiogenesis and provides the impetus as additional targets for the control of angiogenesis in pathological pregnancy.