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GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway
Polycystic ovary syndrome (PCOS) is a gynaecological endocrine disease. The objective of the present study was to investigate the role of GTPase immunity-associated protein (GIMAP) 7 in PCOS. A PCOS rat model was established using dehydroepiandrosterone injection. The data showed that GIMAP7 was mai...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9801623/ https://www.ncbi.nlm.nih.gov/pubmed/36581994 http://dx.doi.org/10.1186/s13048-022-01092-z |
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author | Xu, Anran Fan, Yuanyuan Liu, Song Sheng, Lianbing Sun, Yanyan Yang, Huijun |
author_facet | Xu, Anran Fan, Yuanyuan Liu, Song Sheng, Lianbing Sun, Yanyan Yang, Huijun |
author_sort | Xu, Anran |
collection | PubMed |
description | Polycystic ovary syndrome (PCOS) is a gynaecological endocrine disease. The objective of the present study was to investigate the role of GTPase immunity-associated protein (GIMAP) 7 in PCOS. A PCOS rat model was established using dehydroepiandrosterone injection. The data showed that GIMAP7 was mainly located in granulosa cells and was abundantly expressed in the ovarian granulosa cells of PCOS rats. GIMAP7 silencing decreased blood glucose levels, HOMA-IR scores, and number of cystic follicles. In addition, GIMAP7 silencing corrected erratic oestrous cycles, inhibited apoptosis and reduced c-caspase-3 protein expression in the ovarian tissues of PCOS rats. GIMAP7 silencing reduced malondialdehyde (MDA) but increased glutathione (GSH) and superoxide dismutase (SOD) levels in the serum and ovarian tissues of PCOS rats. The effects of GIMAP7 were further investigated in human ovarian granulosa KGN cells. GIMAP7 silencing increased the viability, promoted proliferation, and increased the percentage of S-phase KGN cells. The apoptosis rate was significantly decreased by GIMAP7 silencing. GIMAP7 also inhibited oxidative stress in KGN cells, resulting in decreased levels of reactive oxygen species (ROS) and MDA and increased levels of GSH and SOD. Notably, GIMAP7 inhibited the sonic hedgehog (SHH) signalling pathway, and GIMAP7 silencing increased the expression of the SHH signalling pathway downstream genes SHH, SMO, and Gli1. Inhibition of the SHH signalling pathway using cyclopamine reduced the effect of GIMAP7 silencing on KGN cells. This study proved that GIMAP7 promotes oxidative stress and apoptosis in ovarian granulosa cells in PCOS by inhibiting the SHH signalling pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-022-01092-z. |
format | Online Article Text |
id | pubmed-9801623 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98016232022-12-31 GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway Xu, Anran Fan, Yuanyuan Liu, Song Sheng, Lianbing Sun, Yanyan Yang, Huijun J Ovarian Res Research Polycystic ovary syndrome (PCOS) is a gynaecological endocrine disease. The objective of the present study was to investigate the role of GTPase immunity-associated protein (GIMAP) 7 in PCOS. A PCOS rat model was established using dehydroepiandrosterone injection. The data showed that GIMAP7 was mainly located in granulosa cells and was abundantly expressed in the ovarian granulosa cells of PCOS rats. GIMAP7 silencing decreased blood glucose levels, HOMA-IR scores, and number of cystic follicles. In addition, GIMAP7 silencing corrected erratic oestrous cycles, inhibited apoptosis and reduced c-caspase-3 protein expression in the ovarian tissues of PCOS rats. GIMAP7 silencing reduced malondialdehyde (MDA) but increased glutathione (GSH) and superoxide dismutase (SOD) levels in the serum and ovarian tissues of PCOS rats. The effects of GIMAP7 were further investigated in human ovarian granulosa KGN cells. GIMAP7 silencing increased the viability, promoted proliferation, and increased the percentage of S-phase KGN cells. The apoptosis rate was significantly decreased by GIMAP7 silencing. GIMAP7 also inhibited oxidative stress in KGN cells, resulting in decreased levels of reactive oxygen species (ROS) and MDA and increased levels of GSH and SOD. Notably, GIMAP7 inhibited the sonic hedgehog (SHH) signalling pathway, and GIMAP7 silencing increased the expression of the SHH signalling pathway downstream genes SHH, SMO, and Gli1. Inhibition of the SHH signalling pathway using cyclopamine reduced the effect of GIMAP7 silencing on KGN cells. This study proved that GIMAP7 promotes oxidative stress and apoptosis in ovarian granulosa cells in PCOS by inhibiting the SHH signalling pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-022-01092-z. BioMed Central 2022-12-30 /pmc/articles/PMC9801623/ /pubmed/36581994 http://dx.doi.org/10.1186/s13048-022-01092-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Xu, Anran Fan, Yuanyuan Liu, Song Sheng, Lianbing Sun, Yanyan Yang, Huijun GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway |
title | GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway |
title_full | GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway |
title_fullStr | GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway |
title_full_unstemmed | GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway |
title_short | GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway |
title_sort | gimap7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9801623/ https://www.ncbi.nlm.nih.gov/pubmed/36581994 http://dx.doi.org/10.1186/s13048-022-01092-z |
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