Upregulation of P27Kip1 by mitomycin C induces fibroblast apoptosis and reduces epidural fibrosis.

: Fibroblast excessive proliferation is considered as one of the major reasons of epidural fibrosis after laminectomy. Recent studies have shown that mitomycin C (MMC) could successfully reduce the formation of epidural fibrosis by inducing fibroblasts apoptosis. However, the detailed mechanism was still unclear. Increasing evidence indicated that P27Kip1 (P27) could result in apoptotic cell death in various cells. In this study, we investigated whether MMC could induce fibroblasts apoptosis and reduce epidural fibrosis by regulating P27. Western blot analysis, Hoechst staining, Flow cytometry, and Cell Counting Kit-8 (CCK-8) assay were used to detect the effect of MMC on fibroblasts apoptosis by regulating P27 expression in vitro. Moreover, histological and immunohistochemical assays were used to evaluate the effect of MMC on reducing epidural fibrosis by regulating P27 expression in rats. The results showed that MMC could induce fibroblasts apoptosis and upregulate P27 expression in vitro. Knockdown of P27 partially attenuated MMC-induced expressions of P27 and cleaved PARP as well as increased the cell viability. MMC could reduce epidural fibrosis in a dose-dependent manner in rats by histological analysis. The expression of P27 was increased by MMC treatment as shown by immuohistochemical analysis. In conclusion, this study demonstrated that MMC could upregulate P27 expression, which subsequently induced fibroblasts apoptosis and reduced epidural fibrosis.