Resistin Modulates Low-Density Lipoprotein Cholesterol Uptake in Human Placental Explants via PCSK9.

Autor: Nava-Salazar S; Department of Immunobiochemistry, Instituto Nacional de Perinatologia, Mexico City, Mexico., Flores-Pliego A; Department of Immunobiochemistry, Instituto Nacional de Perinatologia, Mexico City, Mexico., Pérez-Martínez G; Department of Immunobiochemistry, Instituto Nacional de Perinatologia, Mexico City, Mexico., Parra-Hernández S; Department of Immunobiochemistry, Instituto Nacional de Perinatologia, Mexico City, Mexico., Vanoye-Carlo A; Neuroscience Laboratory, Instituto Nacional de Pediatría, Mexico City, Mexico., Ibarguengoitia-Ochoa F; Department of Obstetrics, Instituto Nacional de Perinatologia, Mexico City, Mexico., Perichart-Perera O; Department of Nutrition and Bioprogramming, Instituto Nacional de Perinatologia, Mexico City, Mexico., Reyes-Muñoz E; Coordination of Gynecologic and Perinatal Endocrinology, Instituto Nacional de Perinatologia, Mexico City, Mexico., Solis-Paredes JM; Department of Human Genetics and Genomics, Instituto Nacional de Perinatologia, Mexico City, Mexico., Espino Y Sosa S; Clinical Research Branch, Instituto Nacional de Perinatologia, Mexico City, Mexico., Estrada-Gutierrez G; Research Direction, Instituto Nacional de Perinatologia, Mexico City, Mexico. gpestrad@gmail.com.
Jazyk: angličtina
Zdroj: Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2022 Nov; Vol. 29 (11), pp. 3242-3253. Date of Electronic Publication: 2022 Apr 25.
DOI: 10.1007/s43032-022-00943-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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