Cargando…
Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction
Aging has been deemed the primary factor in erectile dysfunction (ED). Herein, age-related changes in the erectile response and histomorphology were detected, and the relationship between aging and ED was investigated based on gene expression levels. Thirty male Sprague–Dawley (SD) rats were randoml...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831074/ https://www.ncbi.nlm.nih.gov/pubmed/35154570 http://dx.doi.org/10.1155/2022/6831779 |
_version_ | 1784648421403000832 |
---|---|
author | Hu, Daoyuan Ge, Yunlong Cui, Yubin Li, Ke Chen, Jialiang Zhang, Chi Liu, Qiwei He, Lizhao Chen, Weijun Chen, Jun Hu, Cheng Xiao, Hengjun |
author_facet | Hu, Daoyuan Ge, Yunlong Cui, Yubin Li, Ke Chen, Jialiang Zhang, Chi Liu, Qiwei He, Lizhao Chen, Weijun Chen, Jun Hu, Cheng Xiao, Hengjun |
author_sort | Hu, Daoyuan |
collection | PubMed |
description | Aging has been deemed the primary factor in erectile dysfunction (ED). Herein, age-related changes in the erectile response and histomorphology were detected, and the relationship between aging and ED was investigated based on gene expression levels. Thirty male Sprague–Dawley (SD) rats were randomly divided into 6 groups, and intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured. Subsequently, the corpus cavernosum (CC) was harvested and prepared for histological examinations of apoptosis, oxidative stress (OS), and fibrosis. Then, the microarray dataset (GSE10804) was analyzed to identify differentially expressed genes (DEGs) in ED progression, and hub genes were selected. In addition, aged CC smooth muscle cells (CCSMCs) were isolated to evaluate the function of the hub gene by siRNA interference, qRT–PCR, immunofluorescence staining, enzyme-linked immunosorbent assay, western blot analysis, CCK-8 assay, EdU staining, and flow cytometry approaches. The ICP/MAP and smooth muscle cell (SMC)/collagen ratios declined with aging, while apoptosis and OS levels increased with aging. The enriched functions and pathways of the DEGs were investigated, and 15 hub genes were identified, among which IGFBP3 was significantly upregulated. The IGFBP3 upregulation was verified in the CC of aging rats. Furthermore, aged CCSMCs were transfected with siRNA to knock down IGFBP3 expression. The viability and proliferation of the CCSMCs increased, while apoptosis, OS, and fibrosis decreased. Our findings demonstrate that the erectile response of SD rats declines in parallel with enhanced CC apoptosis, OS, and fibrosis with aging. Upregulation of IGFBP3 plays an important role; furthermore, downregulation of IGFBP3 improves the viability and proliferation of CCSMCs and alleviates apoptosis, OS, and fibrosis. Thus, IGFBP3 is a potential therapeutic target for age-related ED. |
format | Online Article Text |
id | pubmed-8831074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-88310742022-02-11 Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction Hu, Daoyuan Ge, Yunlong Cui, Yubin Li, Ke Chen, Jialiang Zhang, Chi Liu, Qiwei He, Lizhao Chen, Weijun Chen, Jun Hu, Cheng Xiao, Hengjun Oxid Med Cell Longev Research Article Aging has been deemed the primary factor in erectile dysfunction (ED). Herein, age-related changes in the erectile response and histomorphology were detected, and the relationship between aging and ED was investigated based on gene expression levels. Thirty male Sprague–Dawley (SD) rats were randomly divided into 6 groups, and intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured. Subsequently, the corpus cavernosum (CC) was harvested and prepared for histological examinations of apoptosis, oxidative stress (OS), and fibrosis. Then, the microarray dataset (GSE10804) was analyzed to identify differentially expressed genes (DEGs) in ED progression, and hub genes were selected. In addition, aged CC smooth muscle cells (CCSMCs) were isolated to evaluate the function of the hub gene by siRNA interference, qRT–PCR, immunofluorescence staining, enzyme-linked immunosorbent assay, western blot analysis, CCK-8 assay, EdU staining, and flow cytometry approaches. The ICP/MAP and smooth muscle cell (SMC)/collagen ratios declined with aging, while apoptosis and OS levels increased with aging. The enriched functions and pathways of the DEGs were investigated, and 15 hub genes were identified, among which IGFBP3 was significantly upregulated. The IGFBP3 upregulation was verified in the CC of aging rats. Furthermore, aged CCSMCs were transfected with siRNA to knock down IGFBP3 expression. The viability and proliferation of the CCSMCs increased, while apoptosis, OS, and fibrosis decreased. Our findings demonstrate that the erectile response of SD rats declines in parallel with enhanced CC apoptosis, OS, and fibrosis with aging. Upregulation of IGFBP3 plays an important role; furthermore, downregulation of IGFBP3 improves the viability and proliferation of CCSMCs and alleviates apoptosis, OS, and fibrosis. Thus, IGFBP3 is a potential therapeutic target for age-related ED. Hindawi 2022-02-03 /pmc/articles/PMC8831074/ /pubmed/35154570 http://dx.doi.org/10.1155/2022/6831779 Text en Copyright © 2022 Daoyuan Hu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Hu, Daoyuan Ge, Yunlong Cui, Yubin Li, Ke Chen, Jialiang Zhang, Chi Liu, Qiwei He, Lizhao Chen, Weijun Chen, Jun Hu, Cheng Xiao, Hengjun Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction |
title | Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction |
title_full | Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction |
title_fullStr | Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction |
title_full_unstemmed | Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction |
title_short | Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction |
title_sort | upregulated igfbp3 with aging is involved in modulating apoptosis, oxidative stress, and fibrosis: a target of age-related erectile dysfunction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831074/ https://www.ncbi.nlm.nih.gov/pubmed/35154570 http://dx.doi.org/10.1155/2022/6831779 |
work_keys_str_mv | AT hudaoyuan upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT geyunlong upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT cuiyubin upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT like upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT chenjialiang upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT zhangchi upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT liuqiwei upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT helizhao upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT chenweijun upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT chenjun upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT hucheng upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction AT xiaohengjun upregulatedigfbp3withagingisinvolvedinmodulatingapoptosisoxidativestressandfibrosisatargetofagerelatederectiledysfunction |