Conclusions
HO-1 was overexpressed in PE placenta, in association with reduced STAT3 phosphorylation (Tyr 705). HO-1 inhibits the STAT3 phosphorylation in placental JEG-3 cells under hypoxia. Thus, we speculate that overexpressed HO-1 might contribute to the reduced STAT3 phosphorylation (Tyr 705) and the pathogenesis of preeclampsia.
Material and methods
The present study focused on the role in preeclampsia of heme oxygenase 1 (HO-1), which is an inducible isoform of HO in response to hypoxia, via examining the expression of HO-1 and the expression and phosphorylation (Tyr705) of Signal transducer and activator of transcription (STAT) 3 in preeclamptic placentas via the immunohistochemical method, western blotting assay and RT-qPCR method. Then we investigated the regulation by HO-1 of the expression and phosphorylation of STAT3 in human placental choriocarcinoma JEG-3 cells under hypoxia.
Methods
The present study focused on the role in preeclampsia of heme oxygenase 1 (HO-1), which is an inducible isoform of HO in response to hypoxia, via examining the expression of HO-1 and the expression and phosphorylation (Tyr705) of Signal transducer and activator of transcription (STAT) 3 in preeclamptic placentas via the immunohistochemical method, western blotting assay and RT-qPCR method. Then we investigated the regulation by HO-1 of the expression and phosphorylation of STAT3 in human placental choriocarcinoma JEG-3 cells under hypoxia.
Results
There was upregulation of HO-1 at both mRNA (1.506 ±0.08347 (N = 37) vs. 1.000 ±0.08854 (N = 31), p < 0.0001) and protein (0.630 ±0.155 (N = 35) vs. 0.310 ±0.052, 0.630 ±0.155 (N = 35), p < 0.001) levels and a reduced level of STAT3 phosphorylation (Tyr 705) in the preeclamptic placental tissues, compared to normal placental tissues (0.143 ±0.027 (N = 35) vs. 0.194 ±0.028 (N = 35), p < 0.01). Also, in vitro experiments demonstrated that HO-1 was markedly promoted by hypoxia in human placental choriocarcinoma JEG-3 cells, 6 or 12 h post treatment (p < 0.05 or p < 0.01). However, the STAT3 phosphorylation (Tyr 705) was attenuated by sustained hypoxia (p < 0.01). Moreover, it was demonstrated that HO-1 overexpression significantly inhibited the hypoxia-promoted STAT3 phosphorylation (Tyr 705). Conclusions: HO-1 was overexpressed in PE placenta, in association with reduced STAT3 phosphorylation (Tyr 705). HO-1 inhibits the STAT3 phosphorylation in placental JEG-3 cells under hypoxia. Thus, we speculate that overexpressed HO-1 might contribute to the reduced STAT3 phosphorylation (Tyr 705) and the pathogenesis of preeclampsia.