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Evidence of type I and type II transforming growth factor-beta receptors in central nervous tissues: changes induced
D Vivien1, M Bernaudin, A Buisson
1Université de Caen, CNRS UMR 6551, Laboratoire de Neurosciences, France.
Abstract:
The peptides of the transforming growth factor-beta (TGF-beta) family transduce their signal through ligand-induced heteromeric complexes that consist of type I and type II serine/threonine kinases. Both TGF-beta receptors are abundant in many peripheral tissues, but clear evidence of their expression in cortical astrocytes and neurons has not been published so far. In this study, we investigated the expression of type I and type II TGF-beta receptors and their potential ligands (TGF-beta1, TGF-beta2, and TGF-beta3) in the CNS by using RT-PCR and immunohistochemistry. Moreover, to further the study of those cell types that exhibit TGF-beta isoforms and related receptors, we examined through the use of RT-PCR whether cortical neurons and astrocytes in culture express the mRNAs for TGF-betas and their receptors. We show that the three TGF-beta isoform mRNAs are present in the CNS. However, although astrocytes in culture display all three isoforms, neurons in culture express only TGF-beta2. We have demonstrated that both type I and type II TGF-beta receptor mRNAs and proteins are present in the CNS and in cultures of cortical neurons and astrocytes. Thus, TGF-betas may act as autocrine and paracrine signals in the CNS between both neurons and astrocytes via the same receptor systems as those found in peripheral tissues. TGF-beta1 has been shown to be induced following hypoxic-ischemic brain injury and may play a critical role in the pathophysiology of degenerative processes in the CNS. In the present investigation, we confirmed that the expression of TGF-beta1 was increased markedly up until 24 h and thereafter was stable over the first 3 days following permanent occlusion of the middle cerebral artery in mice. However, whereas the expression of the type I TGF-beta receptor was not altered by the ischemic insult, the pattern of the type II TGF-beta receptors 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 clearly demonstrates that a knowledge of the expression of ligand-specific receptors following brain injury is a fundamental step in clarifying the involvement of cytokines in neurodegenerative diseases.
Insights
Transforming growth factor-beta (TGF-beta) signaling components are present in the central nervous system (CNS). This study investigates their expression in neurons and astrocytes, revealing potential roles in neurodegeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Transforming growth factor-beta (TGF-beta) signaling is crucial in many tissues, mediated by type I and type II serine/threonine kinase receptors.
- While TGF-beta receptors are common in peripheral tissues, their presence in central nervous system (CNS) cortical astrocytes and neurons remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression of TGF-beta receptors (type I and II) and their ligands (TGF-beta1, TGF-beta2, TGF-beta3) within the CNS.
- To determine if cortical neurons and astrocytes express these TGF-beta signaling components.
- To examine the impact of ischemic injury on TGF-beta signaling in the CNS.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect mRNA expression.
- Immunohistochemistry was employed to visualize protein localization.
- Primary cultures of cortical neurons and astrocytes were utilized.
- A mouse model of middle cerebral artery occlusion was used to study ischemic injury.
Main Results:
- All three TGF-beta isoforms (TGF-beta1, TGF-beta2, TGF-beta3) mRNAs are present in the CNS.
- Cortical astrocytes express all three isoforms, while neurons express only TGF-beta2.
- Both type I and type II TGF-beta receptor mRNAs and proteins are found in the CNS, including in cultured neurons and astrocytes.
- TGF-beta1 expression significantly increased after ischemic injury, but type I receptor expression remained unchanged, while type II receptor expression was altered in the ischemic area.
Conclusions:
- TGF-betas can function as autocrine and paracrine signals in the CNS, utilizing the same receptor systems as in peripheral tissues.
- The altered expression of TGF-beta type II receptors following ischemic insult suggests a potential disruption in signal transduction, even with ligand presence.
- Understanding ligand-specific receptor expression post-brain injury is vital for elucidating the role of cytokines in neurodegenerative diseases.