| Autor: |
Jing Long, Yan Huang, Zhengshan Tang, Yali Shan, Dou Feng, Wenqin Wang, Juan Liu, Ying Huang, Hang Gu, Dewei Guo, Ruojin Yao, Xin Ni |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Antioxidants, Vol 11, Iss 8, p 1505 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2076-3921 |
| DOI: |
10.3390/antiox11081505 |
| Popis: |
We have previously demonstrated that placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) dysfunction contributes to PE pathogenesis. We sought to elucidate molecular mechanisms underlying 11β-HSD2 dysfunction-induced PE and to seek potential therapeutic targets using a 11β-HSD2 dysfunction-induced PE-like rat model as well as cultured extravillous trophoblasts (EVTs) since PE begins with impaired function of EVTs. In 11β-HSD2 dysfunction-induced PE-like rat model, we revealed that placental mitochondrial dysfunction occurred, which was associated with mitDNA instability and impaired mitochondrial dynamics, such as decreased optic atrophy 1 (OPA1) expression. MitoTEMPO treatment significantly alleviated the hallmark of PE-like features and improved mitDNA stability and mitochondrial dynamics in the placentas of rat PE-like model. In cultured human EVTs, we found that 11β-HSD2 dysfunction led to mitochondrial dysfunction and disrupted mtDNA stability. MitoTEMPO treatment improved impaired invasion and migration induced by 11β-HSD2 dysfunction in cultured EVTs. Further, we revealed that OPA1 was one of the key factors that mediated 11β-HSD2 dysfunction-induced excess ROS production, mitochondrial dysfunction and mtDNA reduction. Our data indicates that 11β-HSD2 dysfunction causes mitochondrial dysfunctions, which impairs trophoblast function and subsequently results in PE development. Our study immediately highlights that excess ROS is a potential therapeutic target for PE. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
