Upregulation of HtrA4 in the placentas of patients with severe pre-eclampsia

Serum HtrA1 is differentially regulated between early-onset and late-onset preeclampsia

“…We have previously reported that in the human, the placenta expresses the highest level of HtrA1 mRNA [26]. It is now known that placental HtrA1 expression increases from the first to the third trimester of pregnancy [27], is abnormally elevated in patients with PE [28,29], and PE placentas have a four-fold increase in HtrA1 mRNA compared to controls [30]. These observations suggest that HtrA1 may contribute to the normal development of the placenta and to the pathogenesis of PE.…”

Functional Antagonism between High Temperature Requirement Protein A (HtrA) Family Members Regulates Trophoblast Invasion

“…To the contrary, hypoxia has been shown to enhance HtrA3 expression in first-trimester villous explants and BeWo cells (22). Inagaki et al (24) have recently reported elevated expression levels of HtrA4, but not HtrA3, in preeclampsia. The discrepancy in the above-mentioned HtrA3 and HtrA4 reports might be due to different assay systems or small patient populations used in the studies.…”

Structural insights into the activation mechanisms of human HtrA serine proteases

“…An elevated level of HtrA3 in maternal serum at 13e14 week of gestation has been correlated with subsequently developed preeclampsia [86,87]. However, Inagaki et al [88] reported elevated levels of HtrA4, but not HtrA3, in preeclampsia. Thus, the cause-and-effect relationship between abnormal HtrA protein expression and the pathogenesis of preeclampsia needs further investigation.…”

“…Thus, it is possible that HtrA1/3 may function antagonistically to HtrA4 during embryo implantation. During normal pregnancy the HtrA4 expression level changes and its aberrations have been correlated with preeclampsia [88,90]. HtrA4 may also, like HtrA1/3, modulate the ECM proteins e it has already been shown that it cleaves fibronectin in vitro [89].…”