Role of microRNA-130b in placental PGC-1?/TFAM mitochondrial biogenesis pathway.

ABSTRACT: Diabetes during pregnancy is associated with abnormal placenta mitochondrial function and increased oxidative stress, which affect fetal development and offspring long-term health. Peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?) is a master regulator of mitochondrial biogenesis and energy metabolism. The molecular mechanisms underlying the regulation of PGC-1? in placenta in the context of diabetes remain unclear. The present study examined the role of microRNA 130b (miR-130b-3p) in regulating PGC-1? expression and oxidative stress in a placental trophoblastic cell line (BeWo). Prolonged exposure of BeWo cells to high glucose mimicking hyperglycemia resulted in decreased protein abundance of PGC-1? and its downstream factor, mitochondrial transcription factor A (TFAM). High glucose treatment increased the expression of miR-130b-3p in BeWo cells, as well as exosomal secretion of miR-130b-3p. Transfection of BeWo cells with miR-130b-3p mimic reduced the abundance of PGC-1?, whereas inhibition of miR-130b-3p increased PGC-1? expression in response to high glucose, suggesting a role for miR-130b-3p in mediating high glucose-induced down regulation of PGC-1? expression. In addition, miR-130b-3p anti-sense inhibitor increased TFAM expression and reduced 4-hydroxynonenal (4-HNE)-induced production of reactive oxygen species (ROS). Taken together, these findings reveal that miR-130b-3p down-regulates PGC-1? expression in placental trophoblasts, and inhibition of miR-130b-3p appears to improve mitochondrial biogenesis signaling and protect placental trophoblast cells from oxidative stress.

SUBMITTER: Jiang S 

PROVIDER: S-EPMC5522006 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature