Transforming growth factor beta isoforms in the adult rat central and peripheral nervous system

Unsicker, Klaus; Flanders, K. C.; Cissel, David S.; Lafyatis, Robert; Sporn, Michael B.

doi:10.1016/0306-4522(91)90082-y

Cited by 292 publications

(175 citation statements)

References 46 publications

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“…28 In the adult brain, TGF-b2 is found in astrocytes as well as in large neurons and cerebellar Purkinje neurons. 30 TGF-b3 is widely distributed throughout the postnatal brains although at very low levels. 27,28 In the cerebellum, TGF-b2 is the predominant isoform produced by Purkinje cells and by both proliferating and postmitotic granular cells.…”

Section: Discussionmentioning

confidence: 99%

Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues

Arndt

Poser

Schubert

et al. 2005

Laboratory Investigation

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The Sloan Kettering Virus (Ski) family of nuclear oncoproteins represses transforming growth factor-b (TGF-b) signaling through inhibition of transcriptional activity of Smad proteins. Here, we report the discovery of a new functional Smad suppressing element on chromosome 18 (Fussel-18). Fussel-18 encodes for a protein of 297 amino acids sharing characteristic structural features, significant homology and similar genomic organization with the homolog Ski family members, Ski and Ski-related novel sequence (Sno). In contrast to Ski and Sno, which are ubiquitously expressed in human tissues, in situ hybridization, RT-PCR, Western blot and immunohistochemistry revealed a highly specific expression pattern for Fussel-18 in neuronal tissues, especially in the cerebellum, the spinal cord and dorsal root ganglia, during both embryogenesis and adult stage. Functionally, we determined interaction of Fussel-18 with Smad 2 and Smad 3 together with an inhibitory activity on TGF-b signaling. Fussel-18 is the first example of a Smad-binding protein with a highly restricted expression pattern within the nervous system.

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Section: Discussionmentioning

confidence: 99%

Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues

Arndt

Poser

Schubert

et al. 2005

Laboratory Investigation

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“…We have found that TGF-␤2 and TGF-␤3 suppress spontaneous motor activity equally, and a considerably higher dose of TGF-␤1 is required to exert a suppressive effect equal to that required for either TGF-␤2 or TGF-␤3 (20). TGF-␤2 and TGF-␤3 are ubiquitously abundant in the rat brain (36), and we have confirmed that TGF-␤1 and TGF-␤2 levels do not change in the brain, even when total TGF-␤ levels increase (unpublished data). In the present study, we demonstrate that injection of TGF-␤3 into the brain alters peripheral energy metabolism to resemble that induced during exercise exhaustion.…”

mentioning

confidence: 89%

“…These isoforms are expressed in several cell types of the CNS, including neurons, astrocytes, and microglia (9). Unsicker et al (36) reported that TGF-␤2 and TGF-␤3 mRNAs are present in all brain areas, including the cerebral cortex, hippocampus, striatum, cerebellum, and brain stem. In this study, we used TGF-␤3 to represent the TGF-␤ isoforms for the following reasons.…”

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confidence: 99%

Intracranial administration of transforming growth factor-β3 increases fat oxidation in rats

Yamazaki

Arai

Matsumura

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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Yamazaki, Hanae, Masanao Arai, Shigenobu Matsumura, Kazuo Inoue, and Tohru Fushiki. Intracranial administration of transforming growth factor-␤3 increases fat oxidation in rats. Am J Physiol Endocrinol Metab 283: E536-E544, 2002. First published May 28, 2002 10.1152/ ajpendo.00094.2001.-The effects of intracranial transforming growth factor (TGF)-␤3 on spontaneous motor activity and energy metabolism were examined in rats. After injection of TGF-␤3 into the cisterna magna of the rat, spontaneous motor activity decreased significantly for 1 h. The intracranial injection of TGF-␤3 produced an immediate decrease in respiratory exchange ratio (RER). No significant changes were observed in energy expenditure. TGF-␤3 induced a significant increase in total fat oxidation and a decrease in total carbohydrate oxidation. Furthermore, the serum substrates associated with fat metabolism were significantly altered in rats injected with TGF-␤3. Both lipoprotein lipase activity in skeletal muscle and the concentration of serum ketone bodies increased, suggesting that the increase in fat oxidation caused by TGF-␤3 may have occurred in the liver and muscle. Intracranial injection of TGF-␤3 appeared to evoke a switch in the energy substrates accessed in energy expenditure. These results suggest that the release of TGF-␤3 in the brain by exercise is a signal for regulating energy consumption. spontaneous motor activity; respiratory exchange ratio; energy metabolism WE HAVE PREVIOUSLY REPORTED that intracranial administration of cerebrospinal fluid (CSF) from exerciseexhausted rats produced a decrease in spontaneous motor activity, whereas CSF from sedentary rats had no such effect (19).

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“…Under normal conditions, TGF-␤1 appears restricted to meningeal cells, choroid plexus epithelial cells, and glial cells, whereas TGF-␤2 and TGF-␤3 are expressed in both glia and neurons (8). TGF-␤1 plays a central role in the response to brain injury and has been implicated in a number of disorders of the CNS, including stroke (9), Parkinson's disease (10), Alzheimer's disease (11), and brain tumors (12).…”

mentioning

confidence: 99%

Bioluminescence imaging of Smad signaling in living mice shows correlation with excitotoxic neurodegeneration

Luo

Lin

Masliah

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The TGF-␤ signaling pathway is a key organizer of injury and immune responses, and recent studies suggest it fulfills critical roles in CNS function and maintenance. TGF-␤ receptor activation results in phosphorylation of Smad proteins, which subsequently translocate to the nucleus to regulate gene transcription by binding to Smad binding elements (SBE). Using SBE-luciferase reporter mice, we recently discovered that the brain has the highest Smad baseline activity of any major organ in the mouse, and we now demonstrate that this signal is primarily localized to pyramidal neurons of the hippocampus. In vivo excitatory stimulation with kainic acid (KA) resulted in an increase in luciferase activity and phosphorylated Smad2 (Smad2P), and nuclear translocation of Smad2P in hippocampal CA3 neurons correlated significantly with luciferase activity. Although this activation was most prominent at 24 h after KA administration in neurons, Smad2P immunoreactivity gradually increased in astrocytes and microglial cells at 3 and 5 days, consistent with reactive gliosis. Bioluminescence measured over the skull in living mice peaked at 12-72 h and correlated with the extent of microglial activation and pathological markers of neurodegeneration 5 days after injury. Treatment with the glutamate receptor antagonist MK-801 strongly reduced bioluminescence and pathology. These results show that Smad2 signaling is a sensitive marker of neuronal activation and CNS injury that can be used to monitor KA-induced neuronal degeneration. This and related mouse models may provide valuable tools to study mechanisms and treatments for neurodegeneration.

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Transforming growth factor beta isoforms in the adult rat central and peripheral nervous system

Cited by 292 publications

References 46 publications

Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues

Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues

Intracranial administration of transforming growth factor-β3 increases fat oxidation in rats

Bioluminescence imaging of Smad signaling in living mice shows correlation with excitotoxic neurodegeneration

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