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Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target

PURPOSE: To screen Zn(2+)‐dependent histone deacetylase (HDAC) 1‐11 in endometriotic cells and then evaluated the HDACs identified from the screening in ovarian endometrioma (OE) and deep endometriotic (DE) lesions, and to evaluate the therapeutic potential of HDAC8 inhibition in mice. METHODS: Quan...

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Autores principales: Zheng, Hanxi, Liu, Xishi, Guo, Sun‐Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10410010/
https://www.ncbi.nlm.nih.gov/pubmed/37564680
http://dx.doi.org/10.1002/rmb2.12531
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author Zheng, Hanxi
Liu, Xishi
Guo, Sun‐Wei
author_facet Zheng, Hanxi
Liu, Xishi
Guo, Sun‐Wei
author_sort Zheng, Hanxi
collection PubMed
description PURPOSE: To screen Zn(2+)‐dependent histone deacetylase (HDAC) 1‐11 in endometriotic cells and then evaluated the HDACs identified from the screening in ovarian endometrioma (OE) and deep endometriotic (DE) lesions, and to evaluate the therapeutic potential of HDAC8 inhibition in mice. METHODS: Quantification of gene and protein expression levels of HDAC1‐11 in endometriotic cells stimulated by TGF‐β1, and immunohistochemistry analysis of Class I HDACs and HDAC6 in OE/DE lesion samples. The therapeutic potential of HDAC8 inhibition was evaluated by a mouse model of deep endometriosis. RESULTS: The screening identified Class I HDACs and HDAC6 as targets of interest. Immunohistochemistry analysis found a significant elevation in HDAC8 immunostaining in both OE and DE lesions, which was corroborated by gene and protein expression quantification. For other Class I HDACs and HDAC6, their lesional expression was more subtle and nuanced. HDAC1 and HDAC6 staining was significantly elevated in DE lesions while HDAC2 and HDAC3 staining was reduced in DE lesions. Treatment of mice with induced deep endometriosis with an HDAC8 inhibitor resulted in significantly longer hotplate latency, a reduction of lesion weight by nearly two‐thirds, and significantly reduced lesional fibrosis. CONCLUSIONS: These findings highlight the progression‐dependent nature of specific HDAC aberrations in endometriosis, and demonstrate, for the first titme, the therapeutic potential of suppressing HDAC8.
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spelling pubmed-104100102023-08-10 Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target Zheng, Hanxi Liu, Xishi Guo, Sun‐Wei Reprod Med Biol Original Articles PURPOSE: To screen Zn(2+)‐dependent histone deacetylase (HDAC) 1‐11 in endometriotic cells and then evaluated the HDACs identified from the screening in ovarian endometrioma (OE) and deep endometriotic (DE) lesions, and to evaluate the therapeutic potential of HDAC8 inhibition in mice. METHODS: Quantification of gene and protein expression levels of HDAC1‐11 in endometriotic cells stimulated by TGF‐β1, and immunohistochemistry analysis of Class I HDACs and HDAC6 in OE/DE lesion samples. The therapeutic potential of HDAC8 inhibition was evaluated by a mouse model of deep endometriosis. RESULTS: The screening identified Class I HDACs and HDAC6 as targets of interest. Immunohistochemistry analysis found a significant elevation in HDAC8 immunostaining in both OE and DE lesions, which was corroborated by gene and protein expression quantification. For other Class I HDACs and HDAC6, their lesional expression was more subtle and nuanced. HDAC1 and HDAC6 staining was significantly elevated in DE lesions while HDAC2 and HDAC3 staining was reduced in DE lesions. Treatment of mice with induced deep endometriosis with an HDAC8 inhibitor resulted in significantly longer hotplate latency, a reduction of lesion weight by nearly two‐thirds, and significantly reduced lesional fibrosis. CONCLUSIONS: These findings highlight the progression‐dependent nature of specific HDAC aberrations in endometriosis, and demonstrate, for the first titme, the therapeutic potential of suppressing HDAC8. John Wiley and Sons Inc. 2023-08-08 /pmc/articles/PMC10410010/ /pubmed/37564680 http://dx.doi.org/10.1002/rmb2.12531 Text en © 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Zheng, Hanxi
Liu, Xishi
Guo, Sun‐Wei
Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target
title Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target
title_full Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target
title_fullStr Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target
title_full_unstemmed Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target
title_short Aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target
title_sort aberrant expression of histone deacetylase 8 in endometriosis and its potential as a therapeutic target
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10410010/
https://www.ncbi.nlm.nih.gov/pubmed/37564680
http://dx.doi.org/10.1002/rmb2.12531
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AT liuxishi aberrantexpressionofhistonedeacetylase8inendometriosisanditspotentialasatherapeutictarget
AT guosunwei aberrantexpressionofhistonedeacetylase8inendometriosisanditspotentialasatherapeutictarget