EVIDENCE OF TYPE-I AND TYPE-II TRANSFORMING-GROWTH-FACTOR-BETA RECEPTORS IN CENTRAL NERVOUS TISSUES - CHANGES INDUCED BY FOCAL CEREBRAL-ISCHEMIA

The peptides of the transforming growth factor-beta (TGF-beta) family transduce their signal through ligand-induced heteromeric complexes th at consist of type I and type II serine/threonine kinases. Both TGF-be ta receptors are abundant in many peripheral tissues, but clear eviden ce of their expression in cortical astrocytes and neurons has not been published so far. In this study, we investigated the expression of ty pe I and type II TGF-beta receptors and their potential ligands (TGF-b eta 1, TGF-beta 2, and TGF-beta 3) in the CNS by using RT-PCR and immu nohistochemistry. Moreover, to further the study of those cell types t hat exhibit TGF-beta isoforms and related receptors, we examined throu gh the use of RT-PCR whether cortical neurons and astrocytes in cultur e express the mRNAs for TGF-beta s and their receptors. We show that t he three TGF-beta isoform mRNAs are present in the CNS. However, altho ugh astrocytes in culture display all three isoforms, neurons in cultu re express only TGF-beta 2. We have demonstrated that both type I and type II TGF-beta receptor mRNAs and proteins are present in the CNS an d in cultures of cortical neurons and astrocytes. Thus, TGF-beta 1 may act as autocrine and paracrine signals in the CNS between both neuron s and astrocytes via the same receptor systems as those found in perip heral tissues. TGF-beta 1 has been shown to be induced following hypox ic-ischemic brain injury and may play a critical role in the pathophys iology of degenerative processes in the CNS. In the present investigat ion, we confirmed that the expression of TGF-beta 1 was increased mark edly up until 24 h and thereafter was stable over the first 3 days fol lowing permanent occlusion of the middle cerebral artery in mice. Howe ver, whereas the expression of the type I TGF-beta receptor was not al tered by the ischemic insult, the pattern of the type II TGF-beta rece ptors was modified dramatically in the ischemic area 3 days after the occlusion, These data show that, even if ligands are present, they may not be able to transduce their signal. Finally, the present study cle arly demonstrates that a knowledge of the expression of ligand-specifi c receptors following brain injury is a fundamental step in clarifying the involvement of cytokines in neurodegenerative diseases.