@Article{biocell.2025.059573,
AUTHOR = {Juan Cheng, Zhiwei Zhao, Ling Wang, Jirui Wen, Yali Miao, Jiang Wu},
TITLE = {The Anti-Senescence Effect and Mechanism of 17β-Estradiol on Pelvic Organ Prolapse Derived Fibroblasts},
JOURNAL = {BIOCELL},
VOLUME = {49},
YEAR = {2025},
NUMBER = {2},
PAGES = {335--348},
URL = {http://www.techscience.com/biocell/v49n2/59698},
ISSN = {1667-5746},
ABSTRACT = { <b>Objectives:</b> Recently, pre-/post-operative Local Estrogen Therapy (LET) has shown effectiveness in alleviating Pelvic Organ Prolapse (POP) symptoms in clinical therapy. However, there is a lack of scientific evidence to support these claims. Therefore, we aimed to explore the anti-senescence effects and mechanisms of 17β-estradiol (E2) on POP-derived fibroblasts. <b>Methods:</b> The primary fibroblast cells were isolated and cultured from the surgical samples of postmenopausal women clinically diagnosed with pelvic organ prolapse (POP) at stages III-IV (quantified using the POP-Q system) and without any other treatment within 6 months. (n = 12, age 50–75). Colorimetric Cell Counting Kit (CCK-8) assay and Senescence-Associated-β-Galactosidase (SA-β-Gal) staining were used to test the cell proliferative capacity and the senescence rate. Western blotting (WB) was used to detect the expression of Collagen Type I (COL-I), Collagen Type III (COL-III), Cyclin-dependent kinase 4 inhibitor A (p16<sup>INK4a</sup>), Cyclin-dependent kinase inhibitor 1A (p21), Tumor Protein 53 (p53), Sirtuin 1 (SIRT-1) and Microtubule-associated protein 1A/1B-light chain 3-I/II (LC3-I/II) protein. A transmission Electron Microscope (TEM) was used to observe the ultrastructure of fibroblasts. <b>Results:</b> The results showed that E2 significantly promoted the proliferation of fibroblasts derived from POP and reduced the staining rate of SA-β-Gal. It markedly enhanced the extracellular matrix proteins COL-I and COL-III, accompanied by inhibition of the senescent maker p16INK4a. Additionally, our results improved the cells’ autophagy and metabolic activity. Additionally, our results indicate the anti-senescence mechanism of E2 through the mediated SIRT-1/p53/p21 axis pathway. <b>Conclusion:</b> We provide preliminary evidence for the anti-aging effects and mechanisms of E2 on POP, hoping to provide a theoretical basis for estrogen against POP senescence and guide the clinical application and local administration of estrogen in POP treatment.},
DOI = {10.32604/biocell.2025.059573}
}