Premium
Early growth response protein 1 (EGR1) regulates pro‐inflammatory gene expression in response to palmitate and TNFa in human placenta cells and is induced in obese placenta
Author(s) -
Saben Jessica Lynn,
Andres Aline,
Borengasser Sarah,
Zhong Ying,
Shankar Kartik
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.109.8
Subject(s) - placenta , tumor necrosis factor alpha , inflammation , egr1 , endocrinology , gene knockdown , biology , medicine , mapk/erk pathway , gene expression , kinase , immunology , microbiology and biotechnology , gene , fetus , biochemistry , pregnancy , genetics
Maternal obesity has been hypothesized to induce a pro‐inflammatory response in the placenta. However, the specific factors contributing to this pro‐inflammatory response are yet to be determined. Our objective was to examine the effects of palmitic acid (PA), tumor necrosis factor alpha (TNFα) or a combination of both (PA + TNFα) on placental trophoblasts (Bewo cells). Microarray analysis revealed distinct gene expression signatures with increased expression of genes regulated by mitogen activated protein kinases (MAPK), or involved in inflammation, and in the immediate‐early response after exposure to PA, TNFα, or PA + TNFα. An immediate‐early response gene, early growth response 1 ( EGR1), showed the largest increase in mRNA following treatment with PA and PA + TNFα and was regulated by transcription factors downstream of MAPKs. Knockdown of EGR1 in placenta cells impaired the pro‐inflammatory response to PA and PA + TNFα. Analysis of term placenta from lean and obese pregnant women showed increased MAPK signaling and EGR1 protein associated with obesity. RNA‐seq analysis also revealed elevated genes involved with inflammation in obese verses lean placenta. Our results indicate that increased circulating fatty acids and inflammatory cytokines associated with obesity, may contribute to inflammation in placenta cells for which EGR1 may be a key regulator. Grant Funding Source : USDA ARS‐CRIS 6251–51000‐007–04S