Traumatic brain injury increases TGF beta RII expression on endothelial cells

Abstract

Transforming growth factor beta (TGFbeta) modulates a variety of growth related functions following traumatic injury. The cellular response to TGFbeta is predominantly mediated through TGFbeta receptor I (TGFbetaRI) and receptor II (TGFbetaRII) on the cell surface and SMAD proteins intracellularly. We investigated the expression of TGFbeta receptors in the acute and chronic phases of a traumatic cerebral injury (TCI) by immunohistochemistry and in cultures of murine brain microvascular endothelial (EN) cells using cytofluorimetry. Here, we report that TGFbetaRII expression significantly increases on brain endothelial cells in the chronic phase of TCI. SMAD3 and SMAD4 protein expression were also upregulated suggesting the activation of TGFbeta receptor intracellular signaling. When TGFbetaRI and TGFbetaRII expression was studied in in vitro cultures of murine brain microvessel EN cells, TGFbetaRII showed increased expression on proliferating cells that are incorporating BrdU. These data show a differential expression of TGFbetaRI and TGFbetaRII on brain microvessel EN cells in the acute and chronic phases of TCI that might be associated with EN proliferation following injury.