Fulvestrant, an estrogen receptor inhibitor, relieves postoperative hemorrhoid edema via up-regulation of miR- 424-5p
Purpose: To investigate estrogen receptor (ER) expression in postoperative hemorrhoid edema tissues, and the likely mechanism involved in fulvestrant-mediated reduction of postoperative hemorrhoid edema.
Methods: One hundred and eighty-five patients admitted to Jinshan Hospital of Fudan University, Shanghai who accepted hemorrhoidectomy were enrolled in this study. Primary cells were extracted from the anal margin tissues of patients for the determination of changes in ERα and vascular endothelial growth factor (VEGF). In vitro cellular experiments were performed in primary vascular endothelial cells to verify whether ER promoted postoperative perianal edema via the miR-424-5p estrogen receptor α gene (ESR1) axis. The cells were exposed to Fulvestrant, estradiol, and miR-424-5p mimic. Changes in expressions of ERα and VEGF were determined.
Results: Fourteen patients (7.57 %), comprising 2 males (2.60 %) and 12 females (11.1 %), developed
postoperative anal margin edema. There was a significant difference in the incidence of postoperative anal edema between males and females (p < 0.05). Both immunohistochemistry and immunoblotting revealed markedly higher ERα levels in postoperative anal edema tissues than in preoperative tissues (p < 0.05). Moreover, ERα level was regulated by estradiol, and miR-424-5p targeted the estrogen receptor α gene (ESR1).
Conclusion: Estradiol inhibits miR-424-5p through ERα in perianal tissues after hemorrhoid surgery. It increases VEGF and promotes perianal edema. However, fulvestrant inhibits ERα, thereby reducing VEGF expression and mitigating postoperative hemorrhoid edema, and therefore, has potential application for the management of postoperative hemorrhoid edema.
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