Elevated HTRA1 and HTRA4 in severe preeclampsia and their roles in trophoblast functions

Aberrant gene expression during placental development may affect fetal growth and contribute to preeclampsia. The high-temperature requirement A (HTRA) family of proteins are serine proteases that may serve in the quality control of misfolded or mislocalized proteins. Recently, the potential involvement of HTRA1 and HTRA4 in the normal development of the placenta and in the pathogenesis of preeclampsia has been reported. The present study collected placental tissues from patients with severe preeclampsia and gestational age-matched control samples. The expression of HTRA1 and HTRA4 was analyzed using reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The human trophoblast line HTR-8 was transfected with HTRA1 or HTRA4, and cell function was assessed. The present study also detected the expression of HTRA1 and HTRA4 in HTR-8/SVneo transfected cells under hypoxia (1% O-2) and further studied the effects of hypoxia on HTR-8 cell migration. HTRA1 and HTRA4 were mainly localized to the cytoplasm of syncytiotrophoblasts. The expression levels of the two genes were elevated in the placental tissues of patients with severe preeclampsia. Finally, it was determined in vitro that ectopic expression of HTRA1 and HTRA4 significantly attenuated HTR-8 cell migration, and elevated HTRA1 limited HTR-8 cell growth. Under hypoxic conditions, the expression levels of HTRA1 and HTRA4 improved significantly. It was hypothesized that the aberrant expression of HTRA1 or HTRA4 may be involved in the onset of preeclampsia, and increased HTRA1 or HTRA4 expression may affect trophoblast functions.