Induction of transforming growth factor beta receptors following focal ischemia in the rat brain

Gabriella Pál, Gábor Lovas, A. Dobolyi

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 (TGFbRIII). 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 TGFb 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.

Original languageEnglish
Article numbere106544
JournalPLoS One
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 5 2014

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Transforming Growth Factor beta Receptors
Middle Cerebral Artery Infarction
transforming growth factor beta
Transforming Growth Factors
ischemia
Rats
Brain
Ischemia
brain
arteries
receptors
Type I Activin Receptors
rats
Signal transduction
Blood vessels
Accessories
transforming growth factors
Neurons
Phosphotransferases
Ligands

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Induction of transforming growth factor beta receptors following focal ischemia in the rat brain. / Pál, Gabriella; Lovas, Gábor; Dobolyi, A.

In: PLoS One, Vol. 9, No. 9, e106544, 05.09.2014.

Research output: Contribution to journalArticle

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