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Upregulated IGFBP3 with Aging Is Involved in Modulating Apoptosis, Oxidative Stress, and Fibrosis: A Target of Age-Related Erectile Dysfunction
- Source :
- Oxidative Medicine and Cellular Longevity, Vol 2022 (2022)
- Publication Year :
- 2022
- Publisher :
- Hindawi, 2022.
-
Abstract
- 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.
- Subjects :
- Male
Aging
QH573-671
Article Subject
Penile Erection
Myocytes, Smooth Muscle
Down-Regulation
Apoptosis
Cell Biology
General Medicine
Transfection
Fibrosis
Biochemistry
Rats
Up-Regulation
Rats, Sprague-Dawley
Disease Models, Animal
Oxidative Stress
Insulin-Like Growth Factor Binding Protein 3
Erectile Dysfunction
Gene Knockdown Techniques
Animals
Cytology
Cells, Cultured
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19420900
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....64825b1a4b9c2f20dda379515b2fd715
- Full Text :
- https://doi.org/10.1155/2022/6831779