Integrative transcriptomic analysis and preclinical validation identify lansoprazole as a therapeutic candidate for preeclampsia
Abstract
Preeclampsia is a pregnancy disorder with often severe consequences across the maternal-fetal dyad and limited treatment options. We performed an integrated meta-analysis of six placental transcriptomic datasets to identify a preeclampsia-specific gene expression signature, revealing dysregulated pathways related to hypoxia, immune dysfunction, and metabolism. Multivariate INTegrative (MINT) analysis was used to establish a smaller predictive signature with potential utility for identifying circulating biomarkers for earlier preeclampsia diagnosis and monitoring disease progression. This preeclampsia signature queried against a transcriptomic database of more than 1,000 compounds identified lansoprazole, a widely used proton pump inhibitor with an established safety profile, as the top-ranked compound based on its ability to reverse the preeclampsia-associated gene expression signature. Protective benefits of lansoprazole were confirmed using a murine model of immune-mediated fetal wastage where treatment overturned elevated soluble FLT1 levels with significantly improved pregnancy outcomes. These findings support further investigation of lansoprazole as a potential therapy for preeclampsia.
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BibTeX
@article{appierdo2026integrative,
title = {{Integrative transcriptomic analysis and preclinical validation identify lansoprazole as a therapeutic candidate for preeclampsia}},
author = {Romina Appierdo and Giang Pham and Ophelia Yin and Alice S. Tang and Tzu-yu Shao and Ashley L. Severance and Bahar Yilmaz and Jakob Einhaus and Ronald J. Wong and Francesco Vallania and Pier Federico Gherardini and Manuela Helmer-Citterich and Brice Gaudillière and Tomiko T. Oskotsky and David K. Stevenson and Sing Sing Way and Marina Sirota},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117963},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03346-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative transcriptomic analysis and preclinical validation identify lansoprazole as a therapeutic candidate for preeclampsia
AU - Romina Appierdo
AU - Giang Pham
AU - Ophelia Yin
AU - Alice S. Tang
AU - Tzu-yu Shao
AU - Ashley L. Severance
AU - Bahar Yilmaz
AU - Jakob Einhaus
AU - Ronald J. Wong
AU - Francesco Vallania
AU - Pier Federico Gherardini
AU - Manuela Helmer-Citterich
AU - Brice Gaudillière
AU - Tomiko T. Oskotsky
AU - David K. Stevenson
AU - Sing Sing Way
AU - Marina Sirota
PY - 2026
DA - 2026/10/30
JO - iScience
DO - 10.1016/j.isci.2026.117963
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03346-8
AB - Preeclampsia is a pregnancy disorder with often severe consequences across the maternal-fetal dyad and limited treatment options. We performed an integrated meta-analysis of six placental transcriptomic datasets to identify a preeclampsia-specific gene expression signature, revealing dysregulated pathways related to hypoxia, immune dysfunction, and metabolism. Multivariate INTegrative (MINT) analysis was used to establish a smaller predictive signature with potential utility for identifying circulating biomarkers for earlier preeclampsia diagnosis and monitoring disease progression. This preeclampsia signature queried against a transcriptomic database of more than 1,000 compounds identified lansoprazole, a widely used proton pump inhibitor with an established safety profile, as the top-ranked compound based on its ability to reverse the preeclampsia-associated gene expression signature. Protective benefits of lansoprazole were confirmed using a murine model of immune-mediated fetal wastage where treatment overturned elevated soluble FLT1 levels with significantly improved pregnancy outcomes. These findings support further investigation of lansoprazole as a potential therapy for preeclampsia.
SN - 2589-0042
ER -