Rui Liu1, Chan Wei2, Qiang Ma3, Weimin Wang4. 1. Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Department of Gynecology, Maternity and Children's Healthcare Hospital of Foshan, Foshan, Guangdong 528000,China. 2. Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. 3. Department of Peripheral Vessels, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. 4. Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: wangweimin1993@sohu.com.
Abstract
BACKGROUND: The present study aims to explore the possible mechanisms of Hippo-YAP1 signaling pathway in the development of severe preeclampsia (sPE). METHODS: A total of 14 pregnancies complicated with severe preeclampsia as well as 14 healthy pregnancies were involved in this research from Department of Obstetrics, the First Affiliated Hospital of Xi'An Jiaotong University, from 15th March 2016 to 15th March 2018. The mRNA levels of YAP1, TAZ, MST1 and MST2 were tested via the RT-qPCR in the placentas between the two groups. Also, the protein expression degrees of YAP1, TAZ, MST 1 and MST 2 were detected using the technology of Western blotting. At the same time, immune-histochemistry method was performed to localize the expression of YAP1, TAZ, MST 1 and MST 2 proteins in the placentas between the two groups. Yes-associated protein expression was also detected in BeWo and HTR-8/SVneo. Overexpressed plasmid and YAP1 si-RNA were transfered into HTR-8/SVneo trophoblast cells. Transwell invasion assay was used to examine the role of YAP1 in the invasion of HTR-8/SVneo trophoblast cells. RESULTS: In comparison with the normal pregnancy placentas, the mRNA levels of YAP (0.659 ± 0.169 vs. 1.758 ± 0.587, P < 0.001) and TAZ (1.148 ± 0.313 vs. 2.894 ± 0.470, P < 0.001) were decreased in the placentas of severe preeclampsia group while the mRNA levels of MST 1 (1.433 ± 0.306 vs. 0.663 ± 0.162, P < 0.001) and MST 2 (1.497 ± 0.378 vs. 0.554 ± 0.130, P < 0.001) were increased. The Western blotting shown that the expression degrees of YAP1 and TAZ proteins were significantly decreased in the placentas of severe preeclampsia, while the expression level of MST 1 and MST 2 was obviously increased. Furthermore, the staining intensity of YAP1 and TAZ were weaker in the placentas of the severe PE group while the staining intensity of MST 1 and MST 2 was significantly stronger in the placentas of the severe PE group. The invasion ability of the HTR-8/SVneo cells in the YAP1-overexpressed group was significantly higher than the corresponding control group ((313.7 ± 5.86) vs.(194.0 ± 4.00), P < 0.05) while the si-YAP1 group was significantly lower than that of the corresponding control group ((81.33 ± 2.52) vs. (204.67 ± 11.02), P < 0.05). CONCLUSIONS: Hippo-YAP1 signaling pathway may play an essential role in the pathogenesis of sPE by regulating the invasion and proliferation of trophoblast.
BACKGROUND: The present study aims to explore the possible mechanisms of Hippo-YAP1 signaling pathway in the development of severe preeclampsia (sPE). METHODS: A total of 14 pregnancies complicated with severe preeclampsia as well as 14 healthy pregnancies were involved in this research from Department of Obstetrics, the First Affiliated Hospital of Xi'An Jiaotong University, from 15th March 2016 to 15th March 2018. The mRNA levels of YAP1, TAZ, MST1 and MST2 were tested via the RT-qPCR in the placentas between the two groups. Also, the protein expression degrees of YAP1, TAZ, MST 1 and MST 2 were detected using the technology of Western blotting. At the same time, immune-histochemistry method was performed to localize the expression of YAP1, TAZ, MST 1 and MST 2 proteins in the placentas between the two groups. Yes-associated protein expression was also detected in BeWo and HTR-8/SVneo. Overexpressed plasmid and YAP1 si-RNA were transfered into HTR-8/SVneo trophoblast cells. Transwell invasion assay was used to examine the role of YAP1 in the invasion of HTR-8/SVneo trophoblast cells. RESULTS: In comparison with the normal pregnancy placentas, the mRNA levels of YAP (0.659 ± 0.169 vs. 1.758 ± 0.587, P < 0.001) and TAZ (1.148 ± 0.313 vs. 2.894 ± 0.470, P < 0.001) were decreased in the placentas of severe preeclampsia group while the mRNA levels of MST 1 (1.433 ± 0.306 vs. 0.663 ± 0.162, P < 0.001) and MST 2 (1.497 ± 0.378 vs. 0.554 ± 0.130, P < 0.001) were increased. The Western blotting shown that the expression degrees of YAP1 and TAZ proteins were significantly decreased in the placentas of severe preeclampsia, while the expression level of MST 1 and MST 2 was obviously increased. Furthermore, the staining intensity of YAP1 and TAZ were weaker in the placentas of the severe PE group while the staining intensity of MST 1 and MST 2 was significantly stronger in the placentas of the severe PE group. The invasion ability of the HTR-8/SVneo cells in the YAP1-overexpressed group was significantly higher than the corresponding control group ((313.7 ± 5.86) vs.(194.0 ± 4.00), P < 0.05) while the si-YAP1 group was significantly lower than that of the corresponding control group ((81.33 ± 2.52) vs. (204.67 ± 11.02), P < 0.05). CONCLUSIONS: Hippo-YAP1 signaling pathway may play an essential role in the pathogenesis of sPE by regulating the invasion and proliferation of trophoblast.
Authors: Karin Engström; Yumjirmaa Mandakh; Lana Garmire; Zahra Masoumi; Christina Isaxon; Ebba Malmqvist; Lena Erlandsson; Stefan R Hansson Journal: Toxics Date: 2021-12-06