title: Induction of transforming growth factor beta receptors following focal ischemia in the rat brain.
abstract: Transforming growth factor-βs (TGF-βs) regulate cellular proliferation, differentiation, and survival. TGF-βs bind to type I (TGF-βRI) and II receptors (TGF-βRII), which are transmembrane kinase receptors, and an accessory type III receptor (TGF-βRIII). TGF-β may utilize another type I receptor, activin-like kinase receptor (Alk1). TGF-β is neuroprotective in the middle cerebral artery occlusion (MCAO) model of stroke. Recently, we reported the expression pattern of TGF-β1-3 after MCAO. To establish how TGF-βs exert their actions following MCAO, the present study describes the induction of TGF-βRI, RII, RIII and Alk1 at 24 h, 72 h and 1 mo after transient 1 h MCAO as well as following 24 h permanent MCAO using in situ hybridization histochemistry. In intact brain, only TGF-βRI had significant expression: neurons in cortical layer IV contained TGF-βRI. At 24 h after the occlusion, no TGF-β receptors showed induction. At 72 h following MCAO, all four types of TGF-β receptors were induced in the infarct area, while TGF-βRI and RII also appeared in the penumbra. Most cells with elevated TGF-βRI mRNA levels were microglia. TGF-βRII co-localized with both microglial and endothelial markers while TGF-βRIII and Alk1 were present predominantly in endothels. All four TGF-β receptors were induced within the lesion 1 mo after the occlusion. In particular, TGF-βRIII was further induced as compared to 72 h after MCAO. At this time point, TGF-βRIII signal was predominantly not associated with blood vessels suggesting its microglial location. These data suggest that TGF-β receptors are induced after MCAO in a timely and spatially regulated fashion. TGF-β receptor expression is preceded by increased TGF-β expression. TGF-βRI and RII are likely to be co-expressed in microglial cells while Alk1, TGF-βRII, and RIII in endothels within the infarct where TGF-β1 may be their ligand. At later time points, TGF-βRIII may also appear in glial cells to potentially affect signal transduction via TGF-βRI and RII.
authors.affiliation: Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pál
authors.affiliation: Department of Neurology, Semmelweis University, Budapest, Hungary; Department of Neurology, Jahn Ferenc Teaching Hospital, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Lovas
authors.affiliation: Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary; Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary.
authors.forename: Arpád
authors.initials: A
authors.lastname: Dobolyi
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007511:Ischemia / Q000235:genetics* / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta