Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity
Vascular remodeling during microgravity exposure results in postflight cardiovascular deconditioning and orthostatic intolerance in astronauts. To clarify the underlying mechanism, we investigated whether estrogen receptor α (ERα)-NRF1-OMI-mitophagy signaling was involved in the dedifferentiation an...
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| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.1039913/full |
| _version_ | 1797988906036101120 |
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| author | Min Jiang Zifan Liu Zifan Liu Junjie Shao Junjie Shao Jingjing Zhou Jingjing Zhou Haiming Wang Haiming Wang Chao Song Chao Song Xin Li Lin Wang Qiang Xu Xiaojuan Liu Lejian Lin Ran Zhang Ran Zhang Ran Zhang |
| author_facet | Min Jiang Zifan Liu Zifan Liu Junjie Shao Junjie Shao Jingjing Zhou Jingjing Zhou Haiming Wang Haiming Wang Chao Song Chao Song Xin Li Lin Wang Qiang Xu Xiaojuan Liu Lejian Lin Ran Zhang Ran Zhang Ran Zhang |
| author_sort | Min Jiang |
| collection | DOAJ |
| description | Vascular remodeling during microgravity exposure results in postflight cardiovascular deconditioning and orthostatic intolerance in astronauts. To clarify the underlying mechanism, we investigated whether estrogen receptor α (ERα)-NRF1-OMI-mitophagy signaling was involved in the dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) under simulated microgravity. Phenotypic markers, mtDNA copy number and mitochondrial biogenesis, mitochondrial dynamics and mitophagy in rat thoracic artery smooth muscle cells were examined. Four-week hindlimb unweighting (HU) was used to simulate microgravity in rats and 10% serum was used to induce VSMCs dedifferentiation in vitro. The effects of ERα-NRF1-OMI signaling on mitophagy, phenotypic switching and proliferation of VSMCs, and cerebrovascular remodeling in HU rats were studied by genetic manipulation and chronic drug intervention. We found that ERα is positively associated with contractile phenotype switching but inversely correlated with synthetic phenotype switching and proliferation of VSMCs both in vivo and in vitro. During the dedifferentiation process of VSMCs, reduced mtDNA copy number, disturbed mitochondrial biogenesis and respiration, and perturbed fission-fusion-mitophagy signaling were detected, which were reversed by ERα overexpression. Mechanistically, the ERα downstream protein OMI preserved the mitochondrial Parkin level by increasing its protein stability, thereby protecting mitophagy. In line with this, we found that activating ERα signaling by propyl pyrazole triol (PPT) could alleviate the synthetic phenotype switching and proliferation of HU rat cerebral VSMCs by reestablishing fission-fusion-mitophagy hemostasis. The current study clarified a novel mechanism by which inhibited ERα-NRF1-OMI-mitophagy signaling resulted in synthetic phenotype switching and proliferation of VSMCs and cerebrovascular remodeling under simulated microgravity. |
| first_indexed | 2024-04-11T08:11:35Z |
| format | Article |
| id | doaj.art-7202f1c8340844e3a27ae8a7e1e560ee |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-11T08:11:35Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-7202f1c8340844e3a27ae8a7e1e560ee2022-12-22T04:35:21ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-11-011310.3389/fphys.2022.10399131039913Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravityMin Jiang0Zifan Liu1Zifan Liu2Junjie Shao3Junjie Shao4Jingjing Zhou5Jingjing Zhou6Haiming Wang7Haiming Wang8Chao Song9Chao Song10Xin Li11Lin Wang12Qiang Xu13Xiaojuan Liu14Lejian Lin15Ran Zhang16Ran Zhang17Ran Zhang18Department of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaGraduate School of Chinese PLA Medical School, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaGraduate School of Chinese PLA Medical School, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaGraduate School of Chinese PLA Medical School, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaGraduate School of Chinese PLA Medical School, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaGraduate School of Chinese PLA Medical School, Beijing, ChinaDepartment of Health Services, The First Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaDepartment of Cardiovascular Medicine, Chinese PLA General Hospital, Beijing, ChinaGraduate School of Chinese PLA Medical School, Beijing, ChinaState Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, ChinaVascular remodeling during microgravity exposure results in postflight cardiovascular deconditioning and orthostatic intolerance in astronauts. To clarify the underlying mechanism, we investigated whether estrogen receptor α (ERα)-NRF1-OMI-mitophagy signaling was involved in the dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) under simulated microgravity. Phenotypic markers, mtDNA copy number and mitochondrial biogenesis, mitochondrial dynamics and mitophagy in rat thoracic artery smooth muscle cells were examined. Four-week hindlimb unweighting (HU) was used to simulate microgravity in rats and 10% serum was used to induce VSMCs dedifferentiation in vitro. The effects of ERα-NRF1-OMI signaling on mitophagy, phenotypic switching and proliferation of VSMCs, and cerebrovascular remodeling in HU rats were studied by genetic manipulation and chronic drug intervention. We found that ERα is positively associated with contractile phenotype switching but inversely correlated with synthetic phenotype switching and proliferation of VSMCs both in vivo and in vitro. During the dedifferentiation process of VSMCs, reduced mtDNA copy number, disturbed mitochondrial biogenesis and respiration, and perturbed fission-fusion-mitophagy signaling were detected, which were reversed by ERα overexpression. Mechanistically, the ERα downstream protein OMI preserved the mitochondrial Parkin level by increasing its protein stability, thereby protecting mitophagy. In line with this, we found that activating ERα signaling by propyl pyrazole triol (PPT) could alleviate the synthetic phenotype switching and proliferation of HU rat cerebral VSMCs by reestablishing fission-fusion-mitophagy hemostasis. The current study clarified a novel mechanism by which inhibited ERα-NRF1-OMI-mitophagy signaling resulted in synthetic phenotype switching and proliferation of VSMCs and cerebrovascular remodeling under simulated microgravity.https://www.frontiersin.org/articles/10.3389/fphys.2022.1039913/fullmicrogravityvascular smooth muscle cellsphenotypic switchingproliferationestrogen receptor αmitophagy |
| spellingShingle | Min Jiang Zifan Liu Zifan Liu Junjie Shao Junjie Shao Jingjing Zhou Jingjing Zhou Haiming Wang Haiming Wang Chao Song Chao Song Xin Li Lin Wang Qiang Xu Xiaojuan Liu Lejian Lin Ran Zhang Ran Zhang Ran Zhang Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity Frontiers in Physiology microgravity vascular smooth muscle cells phenotypic switching proliferation estrogen receptor α mitophagy |
| title | Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity |
| title_full | Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity |
| title_fullStr | Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity |
| title_full_unstemmed | Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity |
| title_short | Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity |
| title_sort | estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the nrf1 omi mitophagy signaling pathway under simulated microgravity |
| topic | microgravity vascular smooth muscle cells phenotypic switching proliferation estrogen receptor α mitophagy |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.1039913/full |
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