Resistin Modulates Low-Density Lipoprotein Cholesterol Uptake in Human Placental Explants via PCSK9.
Sonia Nava-SalazarArturo Flores-PliegoGiovanni Pérez-MartínezSandra Parra-HernándezAmerica Vanoye-CarloFrancisco Ibarguengoitia-OchoaOtilia Perichart-PereraEnrique Reyes-MuñozJuan Mario Solis-ParedesSalvador Espino Y SosaGuadalupe Estrada GutierrezPublished in: Reproductive sciences (Thousand Oaks, Calif.) (2022)
Maternal metabolic status influences pregnancy and, consequently, the perinatal outcome. Resistin is a pro-inflammatory adipokine predominantly expressed and secreted by mononuclear cells, adipose tissue, and placental trophoblastic cells during pregnancy. Recently, we reported an inverse association between maternal resistin levels and fetal low-density lipoprotein cholesterol (LDL-C). Then, in this work, we used a human placental explant model and the trophoblast cell line JEG-3 to evaluate whether resistin affects placental LDL-C uptake. Resistin exposure induced the transcription factor SREBP-2, LDLR, and PCSK9 mRNA expression, and changes at the protein level were confirmed by immunohistochemistry and Western blot. However, for LDLR, the changes were not consistent between mRNA and protein levels. Using a labeled LDL-cholesterol (BODIPY FL LDL), uptake assay demonstrated that the LDL-C was significantly decreased in placental explants exposed to a high dose of resistin and a lesser extent in JEG-3 cells. In summary, resistin induces PCSK9 expression in placental explants and JEG-3 cells, which could be related to negative regulation of the LDLR by lysosomal degradation. These findings suggest that resistin may significantly regulate the LDL-C uptake and transport from the maternal circulation to the fetus, affecting its growth and lipid profile.
Keyphrases
- low density lipoprotein
- induced apoptosis
- cell cycle arrest
- adipose tissue
- high dose
- transcription factor
- endothelial cells
- pregnant women
- oxidative stress
- birth weight
- poor prognosis
- low dose
- binding protein
- body mass index
- induced pluripotent stem cells
- weight loss
- peripheral blood
- pluripotent stem cells
- african american
- drug induced
- dna binding
- gestational age
- stress induced