Characterization and predicted role of the microRNA expression profile in amnion from obese pregnant women.

Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases. The mechanisms underlying this process are poorly understood, but probably include genetic, epigenetic alterations and changes in fetal nutrient supply. We have studied the microRNA (miRNA) expression profile in amnion from obese and control women at delivery to investigate if a specific miRNA signature is associated with obesity. The expression profile of 365 human miRNAs was evaluated with the TaqMan Array in amnion from 10 obese and 5 control (prepregnancy body mass index (BMI) >30 and <25 kg m(-2), respectively) women at delivery. Target genes and miRNA-regulated pathways were predicted by bioinformatics. Anthropometric and biochemical parameters were also measured in mothers and newborns. Seven miRNAs were expressed only in obese women (miR-422b, miR-219, miR-575, miR-523, miR-579, miR-618 and miR-659), whereas 13 miRNAs were expressed at a higher level and 12 miRNAs at a lower level in obese women than in controls. MicroRNAs significantly downregulated the neurotrophin, cancer/ErbB, mammalian target of rapamycin, insulin, adipocytokine, actin cytoskeleton and mitogen-activated protein kinase signaling pathways. In conclusion, we show that the miRNA profile is altered in amnion during obesity and hypothesize that this could affect pathways important for placental growth and function, thereby contributing to an increase in the newborn's risk of future metabolic diseases.

Effects of in vitro nutrient supplementation on polymorphonuclear cell respiratory burst in primary IgA nephropathy.

Since recent findings have pointed out a key role for reactive oxygen species in kidney diseases, we investigated superoxide anion (O2-) and hydrogen peroxide (H2O2) generation by peripheral blood polymorphonuclear cells (PMN) in 20 patients with primary IgA nephropathy (IgAN). Results provided evidence for a significant enhancement of O2- and H2O2 production in IgAN subjects in comparison to patients affected by hypertensive renal injury and healthy donors. Among the IgAN group, the highest oxidative metabolism was observed in patients with severe histologic lesions. On the other hand, in vitro vitamin and/or trace element supplementation to PMN suspensions led to a down modulation of their oxidative responsiveness. These data were further supported by the assessment of O2- release on a kinetic basis. Nutrient pretreatment was in fact able to antagonize either the IgAN-related shortening of the lag period or the increase of maximum O2- production rate following agonist stimulation. Taken together, these findings indicate that an exaggerated PMN oxidative metabolism occurs in IgAN and suggest a potential role for micronutrients in the modulation of PMN metabolic pathway.