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Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome
Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenemia and ovarian antral follicle growth arrest. We have previously demonstrated that androgen-induced exosomal release of miR-379-5p (miR379) from preantral follicle granulosa cells increases the proliferation of target cells via pho...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081157/ https://www.ncbi.nlm.nih.gov/pubmed/37033997 http://dx.doi.org/10.3389/fimmu.2023.1104550 |
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author | Salehi, Reza Asare-Werehene, Meshach Wyse, Brandon A. Abedini, Atefeh Pan, Bo Gutsol, Alex Jahangiri, Sahar Szaraz, Peter Burns, Kevin D. Vanderhyden, Barbara Li, Julang Burger, Dylan Librach, Clifford L. Tsang, Benjamin K. |
author_facet | Salehi, Reza Asare-Werehene, Meshach Wyse, Brandon A. Abedini, Atefeh Pan, Bo Gutsol, Alex Jahangiri, Sahar Szaraz, Peter Burns, Kevin D. Vanderhyden, Barbara Li, Julang Burger, Dylan Librach, Clifford L. Tsang, Benjamin K. |
author_sort | Salehi, Reza |
collection | PubMed |
description | Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenemia and ovarian antral follicle growth arrest. We have previously demonstrated that androgen-induced exosomal release of miR-379-5p (miR379) from preantral follicle granulosa cells increases the proliferation of target cells via phosphoinositide-dependent kinase 1 (PDK1) upregulation. Androgen also increases inflammatory M1 macrophage abundance, but reduces anti-inflammatory M2 polarization in rat antral and preovulatory follicles. However, the role of small extracellular vesicles (sEVs; also known as exosomes) secretion in determining the cellular content and function of miRNAs in exosome-receiving cells is largely unknown. Our objectives were to determine: 1) the regulatory role of granulosa cells (GC)-derived exosomal miR379 on macrophage polarization and ovarian inflammation; 2) whether miR379-induced M1 polarization regulates GC proliferation; and 3) if this regulated process is follicular stage-specific. Compared with non-PCOS subjects, PCOS subjects had a higher M1/M2 ratio, supporting the concept that PCOS is an inflammatory condition. Ovarian overexpression of miR379 increased the number of M1 macrophages and the M1/M2 ratio in preantral follicles specifically. Transfection of macrophages with a miR379 mimic reduced the cellular content of PDK1 and induced M0→M1 polarization; whereas its inhibitor polarized M0→M2. Conditioned media from macrophages transfected with miR379 mimic and follicular fluid from PCOS subjects had higher galectin-3 content, a pro-inflammatory cytokine which specifically suppresses human antral follicle GC proliferation. These results indicate that miR379 inhibits M2 macrophage polarization, a condition which suppresses GC proliferation in a follicle stage-dependent manner, as exhibited in PCOS. |
format | Online Article Text |
id | pubmed-10081157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100811572023-04-08 Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome Salehi, Reza Asare-Werehene, Meshach Wyse, Brandon A. Abedini, Atefeh Pan, Bo Gutsol, Alex Jahangiri, Sahar Szaraz, Peter Burns, Kevin D. Vanderhyden, Barbara Li, Julang Burger, Dylan Librach, Clifford L. Tsang, Benjamin K. Front Immunol Immunology Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenemia and ovarian antral follicle growth arrest. We have previously demonstrated that androgen-induced exosomal release of miR-379-5p (miR379) from preantral follicle granulosa cells increases the proliferation of target cells via phosphoinositide-dependent kinase 1 (PDK1) upregulation. Androgen also increases inflammatory M1 macrophage abundance, but reduces anti-inflammatory M2 polarization in rat antral and preovulatory follicles. However, the role of small extracellular vesicles (sEVs; also known as exosomes) secretion in determining the cellular content and function of miRNAs in exosome-receiving cells is largely unknown. Our objectives were to determine: 1) the regulatory role of granulosa cells (GC)-derived exosomal miR379 on macrophage polarization and ovarian inflammation; 2) whether miR379-induced M1 polarization regulates GC proliferation; and 3) if this regulated process is follicular stage-specific. Compared with non-PCOS subjects, PCOS subjects had a higher M1/M2 ratio, supporting the concept that PCOS is an inflammatory condition. Ovarian overexpression of miR379 increased the number of M1 macrophages and the M1/M2 ratio in preantral follicles specifically. Transfection of macrophages with a miR379 mimic reduced the cellular content of PDK1 and induced M0→M1 polarization; whereas its inhibitor polarized M0→M2. Conditioned media from macrophages transfected with miR379 mimic and follicular fluid from PCOS subjects had higher galectin-3 content, a pro-inflammatory cytokine which specifically suppresses human antral follicle GC proliferation. These results indicate that miR379 inhibits M2 macrophage polarization, a condition which suppresses GC proliferation in a follicle stage-dependent manner, as exhibited in PCOS. Frontiers Media S.A. 2023-03-24 /pmc/articles/PMC10081157/ /pubmed/37033997 http://dx.doi.org/10.3389/fimmu.2023.1104550 Text en Copyright © 2023 Salehi, Asare-Werehene, Wyse, Abedini, Pan, Gutsol, Jahangiri, Szaraz, Burns, Vanderhyden, Li, Burger, Librach and Tsang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Salehi, Reza Asare-Werehene, Meshach Wyse, Brandon A. Abedini, Atefeh Pan, Bo Gutsol, Alex Jahangiri, Sahar Szaraz, Peter Burns, Kevin D. Vanderhyden, Barbara Li, Julang Burger, Dylan Librach, Clifford L. Tsang, Benjamin K. Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome |
title | Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome |
title_full | Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome |
title_fullStr | Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome |
title_full_unstemmed | Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome |
title_short | Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome |
title_sort | granulosa cell-derived mir-379-5p regulates macrophage polarization in polycystic ovarian syndrome |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081157/ https://www.ncbi.nlm.nih.gov/pubmed/37033997 http://dx.doi.org/10.3389/fimmu.2023.1104550 |
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