间充质基质细胞逆转子宫内膜纤维化的机制研究OA
Mechanism of mesenchymal stromal cells reversing fibrosis of the uterine endometrium after injury
为探讨间充质基质细胞(mesenchymal stromal cells,MSCs)对子宫内膜损伤小鼠模型纤维化进程及内膜再生的影响,采用物理搔刮联合脂多糖(LPS)化学诱导建立小鼠子宫内膜损伤模型,单侧给予 MSCs后通过苏木精-伊红(HE)染色和 Masson染色评估内膜形态与胶原沉积;采用 RT-qPCR和免疫荧光法检测上皮标志物 Epcam及胶原蛋白Ⅰ(Col1)的表达;提取原代子宫内膜上皮细胞,检测细胞周期蛋白 p21的表达;通过转录组测序分析及 RT-qPCR验证纤维化相关基因及信号通路.实验结果表明,MSCs增加了子宫内膜厚度与腺体数量(P<0.05),并上调了 Epcam的表达(P<0.01),同时显著降低了子宫胶原纤维沉积(P<0.05)及原代上皮细胞中 p21的表达(P<0.000 1).转录组学分析表明,MSCs通过调控TGF-β通路相关基因,抑制胶原沉积.本研究揭示了 MSCs通过逆转子宫内膜纤维化、促进上皮再生,从而修复子宫损伤,其作用与调控TGF-β/SMAD通路、抑制胶原异常沉积有关.
To investigate the effect of mesenchymal stromal cells(MSCs)on the fibrosis progression and endometrial regeneration in mouse models of endometrial injury,a mouse endometrial injury model was established by physical scraping combined with lipopolysaccharide(LPS)chemical induction,and the endometrium morphology and collagen deposition were evaluated by HE and Masson staining after unilateral administration of MSCs.RT-qPCR and immunofluorescence were used to detect the expression of epithelial markers Epcam and collagen I(Col1).Primary endometrial epithelial cells were isolated to assess p21 expression.Fibrosis-related genes and signaling pathways were validated using transcriptome sequencing and RT-qPCR.The experimental results showed that MSCs increased endometrial thickness and number of glands(P<0.05),up-regulated the expression of Epcam(P<0.01),while significantly reducing uterine collagen fiber deposition(P<0.05)and the expression of p21 in primary epithelial cells(P<0.000 1).Transcriptomic analysis revealed that MSCs attenuated collagen deposition by modulating genes involved in the TGF-β signaling pathway.This study elucidates that MSCs facilitate uterine repair by reversing endometrial fibrosis and promoting epithelial regeneration,and their role is related to the regulation of the TGF-β/SMAD pathway and suppression of aberrant c ollagen accumulation.
李诗琪;党玥;周青青;尚鑫;刘嘉莉
中国药科大学药物代谢动力学重点实验室,南京 210009中国药科大学药物代谢动力学重点实验室,南京 210009中国药科大学药物代谢动力学重点实验室,南京 210009中国药科大学药物代谢动力学重点实验室,南京 210009中国药科大学药物代谢动力学重点实验室,南京 210009
医药卫生
子宫内膜损伤间充质基质细胞胶原纤维TGF-β/SMAD通路
endometrial injurymesenchymal stromal cellscollagen fiberTGF-β/SMAD pathway
《中国药科大学学报》 2026 (3)
360-368,9
国家自然科学基金项目(No.82173882)中国科协青年人才托举项目(2023QNRC001)江苏省自然科学基金项目(BK20220149) This study was supported by the National Natural Science Foundation of China(No.82173882)the Young Elite Scientists Sponsorship Program of China Association for Science and Technology(2023QNRC001)and the Natural Science Foundation of Jiangsu Province(BK20220149)
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