title: 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.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.|Institutes of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Weihua
authors.identifier: 0000-0001-5262-397X
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neuropediatrics, Christian-Albrechts-University of Kiel, Kiel, 24105, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stephani
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lü
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008297:Male; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003292:Convulsants; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C000602391:Zfyve9 protein, rat; D010862:Pilocarpine
keywords: SARA; Smad3; seizure; temporal lobe epilepsy