Abstract
Preeclampsia (PE) is a serious disease during pregnancy that affects approximately eight million mothers and infants worldwide each year and is closely related to abnormal trophoblast function. However, research on placental trophoblast functional abnormalities is insufficient, and the etiology of PE is unclear. Here, we report that the expression of transgelin-2 (TAGLN2) was downregulated in the placenta of patients with PE. In addition, a lack of TAGLN2 significantly reduced the ability of trophoblasts to migrate, invade and fuse. A co-immunoprecipitation (Co-IP) and microscale thermophoresis analysis showed that TAGLN2 bound directly to E-cadherin. A decrease in TAGLN2 expression led to a reduction in cleavage of the E-cadherin extracellular domain, thereby regulating the function of trophoblasts. In addition, we found that a reduction in soluble E-cadherin may also have an effect on blood vessel formation in the placenta, which is necessary for normal placental development. What’s more, the in vivo mouse model provided additional evidence of TAGLN2 involvement in the development of PE. By injecting pregnant mice with Ad-TAGLN2, we successfully generated a human PE-like syndrome that resulted in high blood pressure and some adverse pregnancy outcomes. Overall, the association between TAGLN2 and PE gives a new insight into PE diagnosis and treatment.
Highlights
Preeclampsia (PE) is a serious disease during pregnancy that affects approximately eight million mothers and infants worldwide each year (Fisher, 2015; Burton et al, 2019)
The results showed that TAGLN2 was expressed in different trophoblast subtypes, including villous STBs and CTBs and interstitial extravillous trophoblasts (EVTs) in the decidua (Figure 1A)
Cytotrophoblasts emigrate from the chorionic villi and invade the maternal decidua, and further deeply invade the spiral arteries within the uterine wall
Summary
Preeclampsia (PE) is a serious disease during pregnancy that affects approximately eight million mothers and infants worldwide each year (Fisher, 2015; Burton et al, 2019). This complication is characterized by new onset hypertension (Croke, 2019) and may be accompanied by other serious symptoms, such as thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema and even new onset brain or visual impairment (American College of Obstetricians and Gynecologists, 2013; Poon and Sahota, 2019). TAGLN2-Regulated Trophoblast Impaired in PE (Red-Horse et al, 2004) Both CTBs and STBs play key roles in the development and maintenance of a successful pregnancy. The invasion of shallow CTBs and insufficient repair of the spiral artery are markers of early-onset PE (Brosens et al, 2011)
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