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HtrA1 in placental cell models: A possible role in preeclampsia


Tossetta, Giovanni et al. (2023), HtrA1 in placental cell models: A possible role in preeclampsia, Dryad, Dataset,


Background: The High temperature requirement A 1 (HtrA1) is a multidomain secretory protein with serine-protease activity involved in the regulation of many cellular processes in both physiological and pathological conditions. HtrA1 is normally expressed in human placenta, and its expression is higher in the first trimester compared to the third trimester, suggesting an important role of this serine protease in early phases of human placenta development. The aim of this study was to evaluate the functional role of HtrA1 in in vitro models of human placenta in order to define the role of this serine protease in preeclampsia (PE)

Methods: BeWo, HTR8/SVneo and HUVEC cells expressing HtrA1 and showing a cytoplasm localization of HtrA1 were used as syncytiotrophoblast, cytotrophoblast and placental endothelium models respectively. Oxidative stress was induced treating BeWo and HTR8/SVneo cells with H2O2 to mimic PE conditions in order to evaluate its effect on HtrA1 expression. In addition, HtrA1 overexpression and silencing experiments were performed to evaluate the effects on syncytialization, cell mobility and invasion processes. Finally, human recombinant HtrA1 treatments were performed to study the effects of exogenous HtrA1 on Endoglin, VEGFA, ERK1/2, NF-kB and PCNA that are molecules involved in PE onset

Results: Our main data showed that the oxidative stress significantly increased HtrA1 expression in both BeWo and HTR8/SVneo cells. In addition, we demonstrated that HtrA1 has a pivotal role in cell motility and invasion processes. In particular, HtrA1 overexpression increased while HtrA1 silencing decreased cell motility and invasion in HTR8/SVneo cell model. Finally, we found that hrHtrA1 treatments of HUVEC did not alter the expression of the listed above molecules involved in PE onset; (4) Conclusions: In conclusion, our results suggest an important role of HtrA1 in regulating extravillous cytotrophoblast invasion and motility during early stage of placentation in the first trimester of gestation suggesting a key role of this serine protease in PE onset.


Ministero della Salute, Award: SG-2018–12367994