Cargando…
Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression
The activation of androgen receptor (AR) signaling plays an essential role in both prostate stromal cells and epithelial cells during the development of benign prostatic hyperplasia (BPH). Here we demonstrated that androgen ablation after 5α-reductase inhibitor (5-ARI) treatment induced autophagy in...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864884/ https://www.ncbi.nlm.nih.gov/pubmed/29568063 http://dx.doi.org/10.1038/s41419-018-0415-2 |
_version_ | 1783308577727840256 |
---|---|
author | Jiang, Chen-Yi Yang, Bo-Yu Zhao, Sheng Shao, Si-Hui Bei, Xiao-Yu Shi, Fei Sun, Qian Deng, Zheng Wang, Xiao-Hai Han, Bang-Min Zhao, Fu-Jun Xia, Shu-Jie Ruan, Yuan |
author_facet | Jiang, Chen-Yi Yang, Bo-Yu Zhao, Sheng Shao, Si-Hui Bei, Xiao-Yu Shi, Fei Sun, Qian Deng, Zheng Wang, Xiao-Hai Han, Bang-Min Zhao, Fu-Jun Xia, Shu-Jie Ruan, Yuan |
author_sort | Jiang, Chen-Yi |
collection | PubMed |
description | The activation of androgen receptor (AR) signaling plays an essential role in both prostate stromal cells and epithelial cells during the development of benign prostatic hyperplasia (BPH). Here we demonstrated that androgen ablation after 5α-reductase inhibitor (5-ARI) treatment induced autophagy in prostate stromal fibroblasts inhibiting cell apoptosis. In addition, we found that ATG9A expression was increased after androgen ablation, which facilitated autophagic flux development. Knockdown of ATG9A not only inhibited autophagy notably in prostate stromal fibroblasts, but also reduced the volumes of prostate stromal fibroblast and epithelial cell recombinant grafts in nude mice. In conclusion, our findings suggested that ATG9A upregulation after long-term 5-ARI treatment constitutes a possible mechanism of BPH progression. Thus, combined treatment with 5-ARI and autophagy inhibitory agents would reduce the risk of BPH progression. |
format | Online Article Text |
id | pubmed-5864884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58648842018-06-04 Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression Jiang, Chen-Yi Yang, Bo-Yu Zhao, Sheng Shao, Si-Hui Bei, Xiao-Yu Shi, Fei Sun, Qian Deng, Zheng Wang, Xiao-Hai Han, Bang-Min Zhao, Fu-Jun Xia, Shu-Jie Ruan, Yuan Cell Death Dis Article The activation of androgen receptor (AR) signaling plays an essential role in both prostate stromal cells and epithelial cells during the development of benign prostatic hyperplasia (BPH). Here we demonstrated that androgen ablation after 5α-reductase inhibitor (5-ARI) treatment induced autophagy in prostate stromal fibroblasts inhibiting cell apoptosis. In addition, we found that ATG9A expression was increased after androgen ablation, which facilitated autophagic flux development. Knockdown of ATG9A not only inhibited autophagy notably in prostate stromal fibroblasts, but also reduced the volumes of prostate stromal fibroblast and epithelial cell recombinant grafts in nude mice. In conclusion, our findings suggested that ATG9A upregulation after long-term 5-ARI treatment constitutes a possible mechanism of BPH progression. Thus, combined treatment with 5-ARI and autophagy inhibitory agents would reduce the risk of BPH progression. Nature Publishing Group UK 2018-03-22 /pmc/articles/PMC5864884/ /pubmed/29568063 http://dx.doi.org/10.1038/s41419-018-0415-2 Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Jiang, Chen-Yi Yang, Bo-Yu Zhao, Sheng Shao, Si-Hui Bei, Xiao-Yu Shi, Fei Sun, Qian Deng, Zheng Wang, Xiao-Hai Han, Bang-Min Zhao, Fu-Jun Xia, Shu-Jie Ruan, Yuan Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression |
title | Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression |
title_full | Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression |
title_fullStr | Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression |
title_full_unstemmed | Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression |
title_short | Deregulation of ATG9A by impaired AR signaling induces autophagy in prostate stromal fibroblasts and promotes BPH progression |
title_sort | deregulation of atg9a by impaired ar signaling induces autophagy in prostate stromal fibroblasts and promotes bph progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864884/ https://www.ncbi.nlm.nih.gov/pubmed/29568063 http://dx.doi.org/10.1038/s41419-018-0415-2 |
work_keys_str_mv | AT jiangchenyi deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT yangboyu deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT zhaosheng deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT shaosihui deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT beixiaoyu deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT shifei deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT sunqian deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT dengzheng deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT wangxiaohai deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT hanbangmin deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT zhaofujun deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT xiashujie deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression AT ruanyuan deregulationofatg9abyimpairedarsignalinginducesautophagyinprostatestromalfibroblastsandpromotesbphprogression |