Serum From Preeclamptic Women Triggers Endoplasmic Reticulum Stress Pathway and Expression of Angiogenic Factors in Trophoblast Cells

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art_CASTRO_Serum_From_Preeclamptic_Women_Triggers_Endoplasmic_Reticulum_Stress_2022.PDF (4.44 MB)
Citações na Scopus
5
Tipo de produção
article
Data de publicação
2022
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
CASTRO, Karla R.
PRADO, Karen M.
LORENZON, Aline R.
MARQUES, Aldilane L. X.
SILVA, Elaine C. O.
FONSECA, Eduardo J. S.
Citação
FRONTIERS IN PHYSIOLOGY, v.12, article ID 799653, 13p, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Preeclampsia (PE) is a hypertensive disease of pregnancy-associated with placental cell death and endoplasmic reticulum (ER) stress. It is unknown whether systemic factors aggravate placental dysfunction. We investigated whether serum factors in pregnant women with PE activate ER stress and unfolded protein responses (UPRs) in placental explants and trophoblast cells lineage. We cultured placental explants from third-trimester term placentas from control non-preeclamptic (NPE) pregnant women with serum from women with PE or controls (NPE). In PE-treated explants, there was a significant increase in gene expression of GADD34, CHOP, and SDF2. At the protein level, GRP78, SDF2, p-eIF2 alpha, and p-eIF2 alpha/eIF2 alpha ratio were also augmented in treated explants. Assays were also performed in HTR8/SV-neo trophoblast cell line to characterize the putative participation of trophoblast cells. In PE serum-treated protein levels of p-eIF2a and the ratio p-elF2 alpha/elF2 alpha increased after 12 h of treatment, while the gene expression of GADD34, ATF4, and CHOP was greater than control. Increased expression of SDF2 was also detected after 24 h-cultured HTR8/SV-neo cells. PE serum increased sFLT1 gene expression and decreased PlGF gene expression in placental explants. Morphologically, PE serum increased the number of syncytial knots and reduced placental cell metabolism and viability. Analysis of the serum of pregnant women with PE through Raman spectroscopy showed changes in amino acids, carotenoids, lipids, and DNA/RNA, which may be associated with the induction of ER stress found in chorionic villi treated with this serum. In conclusion, this study provides evidence that the serum of pregnant women with PE may impact placental villi changing its morphology, viability, and secreted functional factors while triggers ER stress and an UPR. The differences between PE and control sera include molecules acting as inducing factors in these processes. In summary, the results obtained in our assays suggest that after the development of PE, the serum profile of pregnant women may be an additional factor that feeds a continuous imbalance of placental homeostasis. In addition, this study may expand the possibilities for understanding the pathogenesis of this disorder.
Palavras-chave
ER stress, UPR pathway, trophoblast cells, pre-eclampsia, angiogenic factors
URI
https://observatorio.fm.usp.br/handle/OPI/46010
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MOG
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - LIM/57