CHARACTERIZATION OF DIFFERENTIALLY EXPRESSED TRANSCRIPTS AND MOLECULAR PATHWAYS UNDERLYING THE POTENTIAL EFFECTS OF METFORMIN ON TREATMENT FOR PREECLAMPSIA

Daniela Alves; Izabela Mamede; Lucio Rezende Queiroz; Glória Regina Franco; Marcelo Rizzatti Luizon

Paper Title

Authors

Daniela Alves
Izabela Mamede
Lucio Rezende Queiroz
Glória Regina Franco
Marcelo Rizzatti Luizon

Modality

Xpress presentation

Subject area

Omics

Publishing Date

26/04/2022

Country of Publishing

Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeetingxp2021/409841-characterization-of-differentially-expressed-transcripts-and-molecular-pathways-underlying-the-potential-effects-

ISBN

978-65-5941-645-5

Keywords

Transcriptome, Metformin, Preeclampsia, Endothelial Dysfunction

Summary

Introduction: Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality, defined as pregnancy-induced hypertension and other clinical criteria, which may include proteinuria. Notably, endothelial dysfunction is a hallmark of the disease. There is currently no therapy that can prevent or cure PE. Pharmacological treatment for PE is limited to managing symptoms through antihypertensive therapy, which prolongs gestation and decreases adverse outcomes. However, 40% of pregnant with PE are nonresponsive to antihypertensive therapy and have been associated with adverse outcomes. Metformin is the first-line oral therapy for type 2 diabetes, and it is also used as a treatment for other diseases, including gestational diabetes. Noteworthy, metformin was shown to reduce secretion of antiangiogenic factors and endothelial dysfunction in primary placental cells and human umbilical vein endothelial cells and, therefore, it has potential to treat PE. However, the mechanisms and molecular pathways underlying these effects are unknown. Methods: We analyzed publicly available RNA-seq data from two studies that examined placental tissues from pregnant with PE and one study that used primary human hepatocytes treated with metformin. Our aim was to first characterize the differentially expressed transcripts in both studies using preeclamptic placentas, and then to search for the overlap of potential transcripts and signaling pathways that could be related to metformin effects on reducing endothelial dysfunction. Transcript pseudo-alignment and quantification was performed with Salmon (v1.5.0) on the GENCODE 33 human annotation and differential expression analysis with DeSeq2 and fishpond, and gene set enrichment analysis was performed using Enrichr and the Bioplant 2019 datasets. Results: Among differentially expressed transcripts upregulated in both studies using preeclamptic placentas, we had found 98 coding transcripts which were previously found to be associated with PE in the literature. These transcripts have role on several different signaling pathways related to PE, and the hypoxia-inducible factor 1 (HIF-1) transcriptional activity in hypoxia ranked first according to p value. From the overlap of the coding transcripts found to be upregulated in all RNA-seq data, two from preeclamptic placentas and one from metformin on hepatocytes, we found four transcripts, namely BHLHE40, DUSP1, ERRFI1 and NRIP1. These transcripts have roles on HIF-1 transcriptional activity in hypoxia, MAP-kinase and ovarian infertility pathways. According to the literature, in PE they are involved in process like response to hypoxia, impaired proliferation and differentiation and also metabolic syndromes. Conclusion: Our novel findings suggest that metformin may have a role on regulation of molecular pathways and genes that are known to be related to the pathophysiology of PE, which may help to guide further functional studies in different cell types.

Title of the Event: X-Meeting XPerience 2021
Title of the Proceedings of the event: X-Meeting presentations
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

ALVES, Daniela et al.. CHARACTERIZATION OF DIFFERENTIALLY EXPRESSED TRANSCRIPTS AND MOLECULAR PATHWAYS UNDERLYING THE POTENTIAL EFFECTS OF METFORMIN ON TREATMENT FOR PREECLAMPSIA.. In: X-Meeting presentations. Anais...São Paulo(SP) AB3C, 2021. Available in: https//www.even3.com.br/anais/xmeetingxp2021/409841-CHARACTERIZATION-OF-DIFFERENTIALLY-EXPRESSED-TRANSCRIPTS-AND-MOLECULAR-PATHWAYS-UNDERLYING-THE-POTENTIAL-EFFECTS-. Access in: 21/12/2024