期刊
CELL CYCLE
卷 18, 期 15, 页码 1714-1726出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2019.1632125
关键词
Gremlin; posterior capsular opacification; epithelial mesenchymal transition; extracellular matrix synthesis
类别
资金
- National Natural Science Foundation of China [81470614]
- National Natural Science Foundation for Young Scientists of China [81470614]
- Fundamental Research Funds for the Central Universities [xjj2018099]
- Natural Science Foundation of Shaanxi Province [2018JQ8021]
- First Affiliated Hospital of Xi'an Jiaotong University Foundation [2016QN-04]
- China Postdoctoral Science Foundation [2018 M633528]
Objective: The present study was conducted to determine the role of gremlin during the development of posterior capsular opacification (PCO) via in vitro and in vivo experiments. Methods: The activation, roles and relationships of the BMPs/Smad1/5, MAPK, FAK and AKT signaling pathways in human lens epithelial cells (HLECs) after gremlin induction were detected by western blotting and real-time PCR. Wound-healing, transwell, capsular bag models and rat PCO models assays were used to test the effects of gremlin on HLECs' migration, proliferation, EMT-specific protein alpha-smooth muscle actin(alpha-SMA?and development of PCO in rats. Results: Our data showed that knockdown of the gremlin inhibited the development of PCO and reduced expression of alpha-SMA in rats. While gremlin did not alter the migration of HLECs, it increased the expression of p-ERK and p-AKT. Knockout of Smad2 or Smad3 inhibited the expression of p-ERK and p-AKT proteins induced by gremlin. Gremlin also reduced BMP4-induced expression of the p-Smad1/5 protein. Finally, knockout of Smad1/5 increased gremlin-induced expression of alpha-SMA, fibronectin and type I collagen (COL-1) in HLECs. Conclusion: These results suggested that gremlin contributed to the development of PCO by promoting LEC proliferation, activation of TGF-beta/Smad, ERK and AKT signaling and inhibition of BMPs/Smad1/5 signaling. Furthermore, inhibiting gremlin effectively impaired both PCO development in rats and EMT in the lens capsule. Thus, our data suggest that gremlin might be a potential target for PCO.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据