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

ABSTRACT: Transforming growth factor-?s (TGF-?s) regulate cellular proliferation, differentiation, and survival. TGF-?s bind to type I (TGF-?RI) and II receptors (TGF-?RII), which are transmembrane kinase receptors, and an accessory type III receptor (TGF-?RIII). TGF-? may utilize another type I receptor, activin-like kinase receptor (Alk1). TGF-? is neuroprotective in the middle cerebral artery occlusion (MCAO) model of stroke. Recently, we reported the expression pattern of TGF-?1-3 after MCAO. To establish how TGF-?s exert their actions following MCAO, the present study describes the induction of TGF-?RI, 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-?RI had significant expression: neurons in cortical layer IV contained TGF-?RI. At 24 h after the occlusion, no TGF-? receptors showed induction. At 72 h following MCAO, all four types of TGF-? receptors were induced in the infarct area, while TGF-?RI and RII also appeared in the penumbra. Most cells with elevated TGF-?RI mRNA levels were microglia. TGF-?RII co-localized with both microglial and endothelial markers while TGF-?RIII and Alk1 were present predominantly in endothels. All four TGF-? receptors were induced within the lesion 1 mo after the occlusion. In particular, TGF-?RIII was further induced as compared to 72 h after MCAO. At this time point, TGF-?RIII signal was predominantly not associated with blood vessels suggesting its microglial location. These data suggest that TGF-? receptors are induced after MCAO in a timely and spatially regulated fashion. TGF-? receptor expression is preceded by increased TGF-? expression. TGF-?RI and RII are likely to be co-expressed in microglial cells while Alk1, TGF-?RII, and RIII in endothels within the infarct where TGF-?1 may be their ligand. At later time points, TGF-?RIII may also appear in glial cells to potentially affect signal transduction via TGF-?RI and RII.

SUBMITTER: Pal G 

PROVIDER: S-EPMC4156357 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature