期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.943127
关键词
foetal growth restriction; intrauterine; hypoxia; zebrafish; Wnt; Stat3; pathway; cardiovascular
资金
- AIRC
- Italian Telethon Foundation [IG-2017-19928]
- UniPD Post-doc Fellow [GGP19287]
- AFM Telethon [BIRD192500]
- ARISLA [23315]
- CARIPARO grant SHoCD, Italian Ministry University Research (MIUR) [PG_63/2020]
- ARCA Foundation, Padua [PRIN 20173ZWACS]
- Registry for cardio-cerebro-vascular pathology, Veneto Region, Venice Italy
- UniPD grant TIGRE (Tackling Intrauterine Growth Restriction Effects)
This study identified the Wnt/β-catenin and Jak/Stat3 pathways as key players in the development of Fetal Growth Restriction (FGR). By using drugs targeting these pathways, the researchers were able to rescue FGR phenotypes in zebrafish models. This data suggests the potential of targeting the Wnt/β-catenin pathway for pharmacological intervention in FGR.
Foetal Growth Restriction (FGR), previously known as Intrauterine Growth Restriction (IUGR), is an obstetrical condition due to placental insufficiency, affecting yearly about 30 million newborns worldwide. In this work, we aimed to identify and pharmacologically target signalling pathways specifically involved in the FGR condition, focusing on FGR-related cardiovascular phenotypes. The transcriptional profile of human umbilical cords from FGR and control cases was compared with the response to hypoxia of zebrafish (Danio rerio) transgenic lines reporting in vivo the activity of twelve signalling pathways involved in embryonic development. Wnt/beta-catenin and Jak/Stat3 were found as key pathways significantly dysregulated in both human and zebrafish samples. This information was used in a chemical-genetic analysis to test drugs targeting Wnt/beta-catenin and Jak/Stat3 pathways to rescue a set of FGR phenotypes, including growth restriction and cardiovascular modifications. Treatments with the Wnt/beta-catenin agonist SB216763 successfully rescued body dimensions, cardiac shape, and vessel organization in zebrafish FGR models. Our data support the Wnt/beta-catenin pathway as a key FGR marker and a promising target for pharmacological intervention in the FGR condition.
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