期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 765, 期 -, 页码 198-208出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2015.08.002
关键词
Mitomycin C; miR-200b; Fibroblasts apoptosis; RhoE; Epidural fibrosis
资金
- National Natural Science Foundation of China [81301550, 81371971, 81171694, 81371968]
- Jiangsu Province Nature Science Foundation [BE2010743]
- Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU [IRT-015]
Mitomycin C (MMC) is known to reduce epidural fibrosis, but the underlying mechanisms have not yet been elucidated. Aberrant miR-200b expressions have been reported in multiple types of fibrotic tissues from many diseases. The aim of this study was to clarify the mechanism by which MMC induces fibroblasts apoptosis and reduces epidural fibrosis. The expression of miR-200b in human fibroblasts was determined after MMC treatment, and the targeted association between miR-200b and RhoE was determined using the luciferase activity assay. The effects of MMC and miR-200b on human fibroblasts apoptosis were evaluated using flow cytometry and western blot analysis. The effects of MMC and miR-200b on epidural fibrosis were evaluated using the Rydell classification, hydroxyproline content, apoptotic cell count and histological analysis. The study revealed that MMC could significantly downregulate miR-200b expression and induce human fibroblasts apoptosis. The direct downregulation of miR-200b could induce human fibroblasts apoptosis. Furthermore, we identified the binding sequence for miR-200b within the 3' untranslated region of RhoE. RhoE was confirmed to be a direct target of miR-200b, and RhoE itself acted as a promoter of fibroblasts apoptosis. The inhibition of miR-200b increased fibroblasts apoptosis and reduced epidural fibrosis in rats, which was in accordance with the effect of MMC. This study suggests that MMC induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b expression and its targeting of RhoE. (C) 2015 Elsevier B.V. All rights reserved.
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