Seizures have been shown to upregulate the expression of numerous extracellular matrix molecules.
Tenascin C (TNC) is an
extracellular matrix protein involved in several physiological roles and in pathological conditions. Though TNC upregulation has been described after
excitotoxins injection, to date there is no research work on the signal transduction pathway(s) participating in TNC
protein overproduction. The aim of this study was to evaluate the role of TGF-β signaling pathway on TNC upregulation. In this study, we used male rats, which were injected with saline or
pilocarpine to induce
status epilepticus (SE) and killed 24h, 3 and 7 days after
pilocarpine administration. For evaluating biochemical changes, we measured
protein content of TNC, TGF-β1 and phospho-Smad2/3 for localization of TNC in coronal brain hippocampus at 24h, 3 and 7 days after
pilocarpine-caused SE. We found a significant increase of TNC
protein content in hippocampal homogenates after 1, 3, and 7 days of
pilocarpine-caused SE, together with an enhancement of TNC immunoreactivity in several hippocampal layers and the dentate gyrus field where more dramatic changes occurred. We also observed a significant enhancement of
protein content of both the TGF-β1 and the critical downstream transduction effector phospho-Smad2/3 throughout the chronic exposure. Interestingly, animals injected with
SB-431542, a TGF-β-type I receptor inhibitor, decreased TNC content in cytosolic fraction and diminished phospho-Smad2/3 content in both cytoplasmic and nuclear fraction compared with
pilocarpine vehicle-injected. These findings suggest the participation of TGF-β signaling pathway on upregulation of TNC which in turn support the idea that misregulation of this signaling pathway produces changes that may contribute to disease.