title: Role of TGF-β signaling pathway on Tenascin C protein upregulation in a pilocarpine seizure model.
abstract: 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.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico.
authors.forename: Octavio
authors.initials: O
authors.lastname: Mercado-Gómez
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Landgrave-Gómez
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico.
authors.forename: Virginia
authors.initials: V
authors.lastname: Arriaga-Avila
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Nebreda-Corona
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF, Mexico. Electronic address: rguevara@unam.mx.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Guevara-Guzmán
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D010862:Pilocarpine; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D012640:Seizures / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D002491:Central Nervous System Agents; D004149:Dioxoles; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D019063:Tenascin; D016212:Transforming Growth Factor beta; D010862:Pilocarpine; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat
keywords: Hippocampus; Phospho-Smad2/3; Pilocarpine; Status epilepticus; Tenascin C; Transforming growth factor β