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Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance
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-...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404992/ https://www.ncbi.nlm.nih.gov/pubmed/36009224 http://dx.doi.org/10.3390/antiox11081505 |
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author | Long, Jing Huang, Yan Tang, Zhengshan Shan, Yali Feng, Dou Wang, Wenqin Liu, Juan Huang, Ying Gu, Hang Guo, Dewei Yao, Ruojin Ni, Xin |
author_facet | Long, Jing Huang, Yan Tang, Zhengshan Shan, Yali Feng, Dou Wang, Wenqin Liu, Juan Huang, Ying Gu, Hang Guo, Dewei Yao, Ruojin Ni, Xin |
author_sort | Long, Jing |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9404992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94049922022-08-26 Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance Long, Jing Huang, Yan Tang, Zhengshan Shan, Yali Feng, Dou Wang, Wenqin Liu, Juan Huang, Ying Gu, Hang Guo, Dewei Yao, Ruojin Ni, Xin Antioxidants (Basel) Article 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. MDPI 2022-07-31 /pmc/articles/PMC9404992/ /pubmed/36009224 http://dx.doi.org/10.3390/antiox11081505 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Long, Jing Huang, Yan Tang, Zhengshan Shan, Yali Feng, Dou Wang, Wenqin Liu, Juan Huang, Ying Gu, Hang Guo, Dewei Yao, Ruojin Ni, Xin Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance |
title | Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance |
title_full | Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance |
title_fullStr | Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance |
title_full_unstemmed | Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance |
title_short | Mitochondria Targeted Antioxidant Significantly Alleviates Preeclampsia Caused by 11β-HSD2 Dysfunction via OPA1 and MtDNA Maintenance |
title_sort | mitochondria targeted antioxidant significantly alleviates preeclampsia caused by 11β-hsd2 dysfunction via opa1 and mtdna maintenance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9404992/ https://www.ncbi.nlm.nih.gov/pubmed/36009224 http://dx.doi.org/10.3390/antiox11081505 |
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