Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome
Abstract Objective Numerous studies have confirmed the correlation of microRNAs (miRNAs) with human disease, yet few have explored the role of miR-135 in preeclampsia (PE). This study intends to discuss miR-135’s function in inflammatory response in PE by modulating proprotein convertase subtilisin/...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-021-00335-x |
| _version_ | 1818440498546737152 |
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| author | Xiaolan Zhao Xun Zhang Zhao Wu Jie Mei Lingling Li Yujue Wang |
| author_facet | Xiaolan Zhao Xun Zhang Zhao Wu Jie Mei Lingling Li Yujue Wang |
| author_sort | Xiaolan Zhao |
| collection | DOAJ |
| description | Abstract Objective Numerous studies have confirmed the correlation of microRNAs (miRNAs) with human disease, yet few have explored the role of miR-135 in preeclampsia (PE). This study intends to discuss miR-135’s function in inflammatory response in PE by modulating proprotein convertase subtilisin/kexin-6 (PCSK6) and NLR pyrin domain containing 3 (NLRP3). Methods The venous blood and placental tissues were collected from PE pregnant women and 25 normal ones. The levels of miR-135, PCSK6 and NLRP3 in placenta tissues of patients were detected. Hypoxia/reoxygenation HTR-8/SVneo and HPT-8 models were established to mimic PE in vitro, and cell proliferation, colony formation, apoptosis rate, invasion, migration and inflammation were detected through gain-of and loss-of-function assays. Results MiR-135 was down-regulated, and PCSK6 and NLRP3 were up-regulated in PE patients. Up-regulating miR-135 or silencing PCSK6 strengthened colony formation ability, viability, invasion and migration ability, and weakened apoptosis and inflammation of H/R-treated HTR-8/SVneo and HPT-8 cells. Inhibition of NLRP3 negated the effects of silenced PCSK6 in H/R-treated HTR-8/SVneo and HPT-8 cells. Conclusions Altogether, we demonstrate that up-regulated miR-135 or reduced PCSK6 attenuates inflammatory response in PE by restricting NLRP3 inflammasome, which provides novel therapy for PE treatment. |
| first_indexed | 2024-12-14T18:13:19Z |
| format | Article |
| id | doaj.art-7bb1499692354553ba4d825204142da8 |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-14T18:13:19Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-7bb1499692354553ba4d825204142da82022-12-21T22:52:14ZengBMCMolecular Medicine1076-15511528-36582021-07-0127111210.1186/s10020-021-00335-xUp-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasomeXiaolan Zhao0Xun Zhang1Zhao Wu2Jie Mei3Lingling Li4Yujue Wang5Genaecology and Obstetrics Department, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s HospitalGenaecology and Obstetrics Department, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s HospitalGenaecology and Obstetrics Department, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s HospitalGenaecology and Obstetrics Department, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s HospitalGenaecology and Obstetrics Department, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s HospitalGenaecology and Obstetrics Department, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s HospitalAbstract Objective Numerous studies have confirmed the correlation of microRNAs (miRNAs) with human disease, yet few have explored the role of miR-135 in preeclampsia (PE). This study intends to discuss miR-135’s function in inflammatory response in PE by modulating proprotein convertase subtilisin/kexin-6 (PCSK6) and NLR pyrin domain containing 3 (NLRP3). Methods The venous blood and placental tissues were collected from PE pregnant women and 25 normal ones. The levels of miR-135, PCSK6 and NLRP3 in placenta tissues of patients were detected. Hypoxia/reoxygenation HTR-8/SVneo and HPT-8 models were established to mimic PE in vitro, and cell proliferation, colony formation, apoptosis rate, invasion, migration and inflammation were detected through gain-of and loss-of-function assays. Results MiR-135 was down-regulated, and PCSK6 and NLRP3 were up-regulated in PE patients. Up-regulating miR-135 or silencing PCSK6 strengthened colony formation ability, viability, invasion and migration ability, and weakened apoptosis and inflammation of H/R-treated HTR-8/SVneo and HPT-8 cells. Inhibition of NLRP3 negated the effects of silenced PCSK6 in H/R-treated HTR-8/SVneo and HPT-8 cells. Conclusions Altogether, we demonstrate that up-regulated miR-135 or reduced PCSK6 attenuates inflammatory response in PE by restricting NLRP3 inflammasome, which provides novel therapy for PE treatment.https://doi.org/10.1186/s10020-021-00335-xPreeclampsiaMicroRNA-135PCSK6NLR pyrin domain containing 3 |
| spellingShingle | Xiaolan Zhao Xun Zhang Zhao Wu Jie Mei Lingling Li Yujue Wang Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome Molecular Medicine Preeclampsia MicroRNA-135 PCSK6 NLR pyrin domain containing 3 |
| title | Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome |
| title_full | Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome |
| title_fullStr | Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome |
| title_full_unstemmed | Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome |
| title_short | Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome |
| title_sort | up regulation of microrna 135 or silencing of pcsk6 attenuates inflammatory response in preeclampsia by restricting nlrp3 inflammasome |
| topic | Preeclampsia MicroRNA-135 PCSK6 NLR pyrin domain containing 3 |
| url | https://doi.org/10.1186/s10020-021-00335-x |
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