Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, China.
J Cell Mol Med. 2021 Dec;25(23):11002-11015. doi: 10.1111/jcmm.17023. Epub 2021 Nov 1.
Intrauterine adhesions (IUAs) severely hamper women's reproductive functions. Human amniotic mesenchymal stromal cell (hAMSC) transplantation is effective in treating IUAs. Here, we examined the function of Notch signalling in IUA treatment with hAMSC transplantation. Forty-five Sprague-Dawley female rats were randomly divided into the sham operation, IUA, IUA + E2, IUA + hAMSCs and IUA + hAMSCs + E2 groups. After IUA induction in the rats, hAMSCs promoted endometrial regeneration and repair via differentiation into endometrial epithelial cells. In all groups, the expression of key proteins in Notch signalling was detected in the uterus by immunohistochemistry. The results indicated Notch signalling activation in the hAMSCs and hAMSCs + E2 groups. We could also induce hAMSC differentiation to generate endometrial epithelial cells in vitro. Furthermore, the inhibition of Notch signalling using the AdR-dnNotch1 vector suppressed hAMSC differentiation (assessed by epithelial and mesenchymal marker levels), whereas its activation using the AdR-Jagged1 vector increased differentiation. The above findings indicate Notch signalling mediates the differentiation of hAMSCs into endometrial epithelial cells, thus promoting endometrial regeneration and repair; Notch signalling could have an important function in IUA treatment.
宫腔粘连(IUAs)严重影响女性生殖功能。人羊膜间充质基质细胞(hAMSC)移植在治疗 IUAs 方面有效。在这里,我们研究了 Notch 信号通路在 hAMSC 移植治疗 IUAs 中的作用。45 只 Sprague-Dawley 雌性大鼠被随机分为假手术、IUA、IUA+E2、IUA+hAMSCs 和 IUA+hAMSCs+E2 组。在大鼠诱导 IUA 后,hAMSCs 通过分化为子宫内膜上皮细胞促进子宫内膜再生和修复。在所有组中,通过免疫组织化学检测子宫中 Notch 信号通路的关键蛋白表达。结果表明 hAMSCs 和 hAMSCs+E2 组中 Notch 信号通路被激活。我们还可以在体外诱导 hAMSC 分化为子宫内膜上皮细胞。此外,使用 AdR-dnNotch1 载体抑制 Notch 信号通路会抑制 hAMSC 分化(通过上皮和间充质标志物水平评估),而使用 AdR-Jagged1 载体激活 Notch 信号通路会增加分化。上述发现表明 Notch 信号通路介导 hAMSC 分化为子宫内膜上皮细胞,从而促进子宫内膜再生和修复; Notch 信号通路在 IUAs 治疗中可能具有重要作用。