癌症研究
旁分泌信号
间充质干细胞
间质细胞
下调和上调
干细胞
细胞生物学
转化生长因子
纤维化
基因敲除
生物
分子生物学
医学
细胞培养
内科学
基因
生物化学
遗传学
受体
作者
Ying Feng,Dan Han,Buzhen Tan
摘要
Endometrial-derived stem cells are key players in endometriosis (EMs) pathogenesis, while the mechanism involved is still unclear. Herein, the role and regulatory mechanism of endometriotic mesenchymal stem cells (ecto-MSCs) in regulating fibrosis during EMs progression were investigated.The mRNA and protein expressions were assessed using qRT-PCR, western blot, and immunofluorescence. Flow cytometry was adopted to analyze the markers of MSCs. Transwell assay was adopted to examine endometriotic stromal cells (ESCs) migration and invasion. The interactions between DNMT3A and RASAL1 were analyzed by ChIP assay. In addition, MSP was employed to detect RASAL1 promoter methylation level.Ecto-MSCs promoted ESCs migration, invasion, and fibrosis process by TGF-β1 paracrine. It was subsequently revealed that TGF-β1 upregulated DNMT3A in ESCs in a SMAD3-dependent manner. As expected, DNMT3A knockdown abolished ecto-MSCs' facilitation on ESCs migration, invasion, and fibrosis process. DNMT3A, as a methyltransferase, reduced RASAL1 expression in TGF-β1-treated ESCs by increasing RASAL1 promoter methylation level. RASAL1, as an antifibrotic protein, was lowly expressed in TGF-β1-treated ESCs, and its overexpression ameliorated TGF-β1-induced increase in ESCs migration, invasion, and fibrosis process.TGF-β1 secreted by ecto-MSCs facilitated fibrogenesis in EMs through SMAD3/DNMT3A-mediated RASAL1 inhibition.
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