Smad anchor for receptor activation contributes to seizures in temporal lobe epilepsy.

Abstract

Smad anchor for receptor activation (SARA) is an important regulator of transforming growth factor β (TGF-β) signaling by recruiting Smad2/3 to TGF-β receptors. Although TGF-β signaling is critically involved in epileptogenesis, whether SARA activation is sufficient to facilitate TGF-β pathway to regulate epilepsy remains unknown. The expression of SARA and downstream Phospho-Smad3 (p-Smad3) was examined in rats with pilocarpine induced epilepsy. Additionally, knockdown of SARA was performed via recombinant lentiviral vector in the pilocarpine-induced rats. Here we show that expressions of SARA and p-Smad3 are increased in the hippocampus as rats subjected to pilocarpine-induced status epilepticus (SE). Both SARA and p-Smad3 are also upregulated in the temporal cortex of epileptic rats. Furthermore, SARA mRNA levels reach peak as early as 6 hr following SE onset and remain elevated in the chronic phase. Transfection of recombinant lentiviral shRNA targeting SARA knocks down SARA expression, attenuates TGF-β/p-Smad3 signaling in the hippocampus, and postpones the SE onset. Our results demonstrate that SARA/Smad3 pathway contributes to mechanism of seizure and SARA in TGF-β signaling may be a potential therapeutic target for epilepsy.