Transforming growth factor-β1 induces fibrosis in rat meningeal mesothelial cells via the p38 signaling pathway

Leptomeningeal fibrosis is important in the pathogenesis of communicating hydrocephalus following subarachnoid hemorrhage; however, the underlying mechanisms of leptomeningeal fibrosis remain largely unclear. In the present study, primary meningeal mesothelial cells (MMCs) were used as a cell model to investigate the effect of transforming growth factor-beta 1 (TGF-beta 1) on leptomeningeal fibrosis. Firstly, primary MMCs were isolated from rat brains and characterized by immunofluorescene, staining positive for keratin and vimentin, but negative for factor VIII. Upon TGF-beta 1 treatment, MMCs were induced to express connective tissue growth factor (CTGF), an indicator of fibrosis, in a dose-dependent manner. Furthermore, p38 mitogen-activated protein kinase (MAPK) signaling was significantly activated by TGF-beta 1. However, in the presence of a p38 MAPK inhibitor, TGF-beta 1-induced CTGF expression was markedly suppressed. Together, these data suggest that TGF-beta 1 could induce fibrosis of MMCs via the p38 MAPK signaling pathway, providing a novel potential target for intervention in TGF-beta 1-induced leptomeningeal fibrosis.