子宫内膜不可逆纤维化修复引起的宫腔粘连（IUA）是女性继发性不孕的主要原因，目前 IUA 的治疗方法有限。越来越多的证据表明竞争性内源性 RNA (ceRNA) 在 IUA 病理学中发挥重要作用。本研究旨在探讨长非编码RNA (lncRNA) 转移相关肺腺癌转录物1 (MALAT1) 相关ceRNA 在IUA 发展中的作用。我们从患有或不患有IUA的患者身上采集子宫内膜组织，并从正常子宫内膜组织中提取子宫内膜基质细胞（ESC）。转化生长因子 β1 (TGF-β1) 用于诱导 ESC 纤维化。转化生长因子 β 受体 1 (TGFβR1)、α-平滑肌肌动蛋白、母亲抗十肢瘫痪 (p-Smad)2/3、I 型胶原蛋白 α 1、MALAT1 和 microRNA (miR)-22- 的磷酸化抑制剂的表达通过逆转录定量聚合酶链反应 (RT-qPCR) 或蛋白质印迹法测量子宫内膜组织和 ESC 中的 3p。进行Pearson相关分析以评估子宫内膜组织中miR-22-3p表达或TGFβR1与MALAT1表达之间的相关性。还通过免疫荧光染色评估了 ESC 中 TGFβR1 的表达。通过荧光原位杂交检查 MALAT1 的位置。进行荧光素酶报告基因测定以验证 MALAT1 或 TGFβR1 与 miR-22-3p 之间的结合关系。通过细胞计数试剂盒 8 测定评估细胞活力。我们的研究结果显示，在IUA子宫内膜组织或TGF-β1刺激的ESC中，lncRNA MALAT1和TGFβR1表达上调，而miR-22-3p表达下调，并且lncRNA MALAT1表达与miR-22-3p表达呈负相关，而与TGFβR1呈正相关。 IUA在子宫内膜组织中的表达。此外，lncRNA MALAT1主要位于ESC的细胞质中，直接靶向miR-22-3p来调节TGFβR1的表达。此外，敲低lncRNA MALAT1通过靶向miR-22-3p对ESCs发挥抗纤维化作用，而miR-22-3p过表达通过与TGFβR1 3'非翻译区结合抑制ESCs纤维化。总的来说，lncRNA MALAT1 通过海绵 miR-22-3p 调节 TGFβR1 和 Smad2/3 来促进子宫内膜纤维化，而抑制 MALAT1 可能是抑制子宫内膜纤维化的一种有前景的治疗选择。© 2024。作者获得独家许可Springer Science Business Media, LLC，隶属于 Springer Nature。

Intrauterine adhesion (IUA) resulting from irreversible fibrotic repair of endometrium is the main cause of secondary infertility in women, and current therapeutic approaches to IUA are limited. Increasing evidence has suggested the important role of competitive endogenous RNA (ceRNA) in IUA pathologies. This study aimed to investigate the long noncoding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-associated ceRNA in IUA development. We harvested endometrial tissues from patients with or without IUA and extracted endometrial stromal cells (ESCs) from normal endometrial tissues. Transforming growth factor β1 (TGF-β1) was used to induce fibrosis in ESCs. The expression of transforming growth factor β receptor 1 (TGFβR1), α-smooth muscle actin, phosphorylated suppressor of mother against decapentaplegic (p-Smad)2/3, collagen type I alpha 1, MALAT1, and microRNA (miR)-22-3p in endometrial tissues and ESCs was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) or western blotting. Pearson's correlation analysis was conducted to assess the correlation between miR-22-3p expression or TGFβR1 and MALAT1 expression in endometrial tissues. The expression of TGFβR1 in ESCs was also evaluated by immunofluorescence staining. The location of MALAT1 was examined by fluorescence in situ hybridization. Luciferase reporter assays were performed to verify the binding relationship between MALAT1 or TGFβR1 and miR-22-3p. Cell viability was assessed via cell counting kit-8 assays. Our findings revealed that lncRNA MALAT1 and TGFβR1 were upregulated while miR-22-3p was downregulated in IUA endometrial tissues or TGF-β1-stimulated ESCs, and lncRNA MALAT1 expression was negatively correlated with miR-22-3p expression while being positively correlated with TGFβR1 expression in IUA endometrial tissues. Additionally, lncRNA MALAT1 was mainly located in the cytoplasm of ESCs and directly targeted miR-22-3p to regulate TGFβR1 expression. Moreover, knockdown of lncRNA MALAT1 exerted anti-fibrotic effects on ESCs by targeting miR-22-3p, and miR-22-3p overexpression inhibited the fibrosis of ESCs by binding to TGFβR1 3'untranslated region. Collectively, lncRNA MALAT1 promotes endometrial fibrosis by sponging miR-22-3p to regulate TGFβR1 and Smad2/3, and inhibition of MALAT1 may represent a promising therapeutic option for suppressing endometrial fibrosis.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.