The role of estrogen-induced DCN gene methylation in the pathogenesis of pelvic organ prolapse
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目的 检测盆腔器官脱垂(POP)患者雌二醇(E2)、核心蛋白聚糖(DCN)基因甲基化水平,并研究其在POP发病机制中的作用.方法 选取2023年1月-2024年1月于宁波大学附属第一医院妇科行盆底重建手术治疗的85例POP患者为研究对象,根据术前激素水平及绝经时间分为绝经后期组(PSM组,44例)和绝经过渡期组(TRM组,41例),另选取同期30例盆腔良性疾病患者为对照组.采用50 nmol/L雌激素(H-EST组)、2 nmol/L 雌激素(L-EST 组)、50 nmol/L 雌激素联合 ER 拮抗(ESR siRNA,H-EST+siER 组)及 siER(siER 组)处理原代成纤维细胞,未行任何处理的原代成纤维细胞为对照(CON组).检测并比较E2、DCN、Ⅰ型胶原酶(COL Ⅰ)、E2受体(ER)、DCN基因甲基化差异.结果 PSM组患者E2、DCN、COL Ⅰ及ER表达均显著低于TRM组和对照组(P＜0.05),DCN甲基化率均显著高于TRM组和对照组(P＜0.05).PSM组和TRM组POP患者E2与DCN、COL Ⅰ均呈正相关关系(rs=0.713、0.654、0.679、0.639,均P＜0.05),与DCN基因甲基化呈负相关关系(rs=-0.821、-0.806,P＜0.05).H-EST 组、L-EST 组细胞 DCN、COL Ⅰ 及 ER 表达均显著低于 CON 组、H-EST+siER 组及siER组(P＜0.05),DCN甲基化率均显著高于CON组、H-EST+siER组及siER组(P＜0.05).结论 POP患者E2及DCN基因甲基化率显著升高,两者呈负相关关系,E2可能通过诱导DCN基因甲基化参与POP发病机制.
Objective To detect the methylation of estradiol(E2)and decorin(DCN)genes in patients with pelvic organ prolapse(POP)and to study their role in the pathogenesis of POP.Methods A total of 85 POP patients who underwent surgery between January 2023 and January 2024 were selected for the postmenopause group(PSM group,n=44)and meno-pausal transition period group(TRM group,n=41),additionally,30 patients with pelvic benign diseases during the same period were selected as the control group.The Primary fibroblasts were treated with 50 nmol/L E2(H-EST group),2 nmol/L E2(L-EST group),and 50 nmol/L E2 in combination with an ER antagonist(ESR siRNA,H-EST+siER group).Detect and compare the methylation differences of the estradiol(E2),DCN,type Ⅰ collagenase(COL Ⅰ),E2 receptor(ER)and DCN genes.Results The expressions of E2,DCN,COL Ⅰ and ER in the PSM group were significantly lower than those in the TRM group and the control group(P＜0.05),Furthermore the DCN methylation rate was significantly higher in the PSM group than in the TRM group and the control group(P＜0.05).In patients with POP in the PSM group and TRM group,E2 was found to be positively correlated with the expression of DCN,COL Ⅰ,and ER(rs=0.713,0.654,0.679,0.639,respectively,all P＜0.05),and negatively correlated with DCN gene methylation(rs=-0.821,-0.806,all P＜0.05).The expressions of DCN,COL Ⅰ and ER in cells of the H-EST group and L-EST group were significantly low-er than those of the CON group,H-EST+siER group and siER group(P＜0.05).Furthermore,the DCN methylation rate was significantly higher than that of the CON group,H-EST+siER group and siER group(P＜0.05).Conclusion The methylation rate of DCN genes and E2 level is markedly elevated in patients with POP,and there is a negative correlation.E2 may play a role in the development of POP by inducing methylation of the DCN gene.
Pelvic organ prolapseEstrogenDecorinMethylationPathogenesis
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