间充质干细胞
微泡
外体
癌症研究
SMAD公司
转化生长因子
医学
小RNA
纤维化
上皮-间质转换
干细胞
细胞生物学
生物
内科学
病理
癌症
基因
转移
生物化学
作者
Huidong Liu,Xiao Zhang,Mengtong Zhang,Sichen Zhang,Jin Li,Yingmin Zhang,Qing-Yu Wang,Jian- Ping Cai,Ke Cheng,Shaowei Wang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-01-19
卷期号:18 (4): 3509-3519
被引量:4
标识
DOI:10.1021/acsnano.3c10884
摘要
Intrauterine adhesions (IUA) refer to adhesions within the uterine cavity and cervix caused by injuries from uterine surgery. They are a significant cause of female infertility. Exosomes derived from mesenchymal stem cells (MSCs) play an active role in the treatment of IUA. However, the mechanism by which they reduce fibrosis in the damaged endometrium remains unclear. In this paper, we demonstrate that exosomes derived from placental mesenchymal stem cells (PMSCs) can restore uterine functions and improve the fertility rate of injured animals. This is achieved by promoting cell proliferation, increasing endometrial thickness, and reversing fibrosis. Regarding the molecular mechanism behind these therapeutic effects, we identify three specific miRNAs, namely, miR-125b-5p, miR-30c-5p, and miR-23a-3p, enriched in PMSC-exosomes, as the key players in the treatment of IUA. Specifically, miR-125b-5p/miR-30c-5p and miR-23a-3p inhibit the expression of smad2 and smad3 by targeting their 3′-untranslated regions, resulting in the downregulation of the transforming growth factor-β (TGF-β)/smad signaling pathway and the reversal of fibrosis. Notably, the safety of PMSC-exosomes in intrauterine treatment was also been confirmed. In conclusion, we illustrate that exosomes derived from PMSCs possess the capability to repair endometrial damage and enhance fertility in injured animals by regulating the TGF-β/smad pathway via miR-125b-5p, miR-30c-5p, and miR-23a-3p. This provides insights into the precision treatment of IUA through exosome-based cell-free therapy.
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