Expression, localization, and function of transforming growth factor-?s in embryonic chick spinal cord, hindbrain, and dorsal root ganglia

Unsicker, Klaus; Meier, Carola; Krieglstein, Kerstin; Sartor, Birgit M.; Flanders, Kathleen C.

doi:10.1002/(sici)1097-4695(199602)29:2<262::aid-neu10>3.0.co;2-d

Cited by 56 publications

(25 citation statements)

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“…Overall the mRNA and protein data are consistent with previous observations that there is consistent co-expression of TGF-β2 in neurons and -β3 in Schwann cells, and there are low levels of TGF-β1 in the unlesioned nervous system (Bottner et al, 2000). Previous published findings also show that that the TGF-β3 mRNA signal in neurons is weak, but neurons are strongly labeled following treatment with NGF or fibroblast growth factor-2 in the presence of Schwann cells (Bottner et al, 2000;Unsicker et al, 1996). This further indicates that different isoforms of TGF-β will express differently at different sites within the peripheral nervous system and may have alternative effects on signaling or cell biology in different disease states.…”

Section: Discussionmentioning

confidence: 82%

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Anjaneyulu

Berent-Spillson

Inoue

et al. 2008

Experimental Neurology

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The mechanism/s leading to diabetic neuropathy are complex. Transforming growth factor-β1 (TGF-β1) has been associated with diabetic nephropathy and retinopathy but not neuropathy. In this study, changes in TGF-β isoforms were examined in-vivo and in-vitro. Two groups of animals, streptozotocin diabetic with neuropathy and non-diabetic controls were examined at 4 weeks (n=10/ group) and 12 weeks (n=8/group). In diabetic DRG using quantitative real-time PCR (QRT-PCR), TGF-β1 and TGF-β2 mRNA, but not TGF-β3, was increased at 4 and 12 weeks. In sciatic nerve TGF-β3 mRNA was primarily increased. Immunohistochemistry (DRG) and immunoblotting (sciatic nerve) showed similar differential protein expression. In sciatic nerve TGF-β formed homoand heterodimers, of which β 2 /β 3 , β 1 /β 1 , and β 1 /β 3 were significantly increased, while that of the TGF-β 2 /β 2 homodimer was decreased, in diabetic compared to non-diabetic rats. In-vitro, pretreatment of embryonic DRG with TGF-β neutralizing antibody prevents the increase in total TGF-β protein observed with high glucose using immunoblotting. In high glucose conditions, combination with TGF-β2 > β1 increases the percent of cleaved caspase-3 compared to high glucose alone and TGF-β neutralizing antibody inhibits this increase. Furthermore, consistent with the findings in diabetic DRG and nerve, TGF-β isoforms applied directly in vitro reduce neurite outgrowth, and this effect is partially reversed by TGF-β neutralizing antibody. These findings implicate upregulation of TGF-β in experimental diabetic peripheral neuropathy and indicate a novel mechanism of cellular injury related to elevated glucose levels. In combination, these findings indicate a potential new target for treatment of diabetic peripheral neuropathy.

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Section: Discussionmentioning

confidence: 82%

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Anjaneyulu

Berent-Spillson

Inoue

et al. 2008

Experimental Neurology

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“…Platelets store and release many different growth factors affecting wound healing 12,13 . Among others, TGF‐β or PDGF stored in the α‐granules of platelets are important mediators for the initiation of healing, 14 for example, in tendons, 15 bones, 16 nerves, 17 mesentery, 18 and skin 19 . So the application of these growth factors or platelets is conceivable in a wide range of tissues.…”

Section: Discussionmentioning

confidence: 99%

Preparation of autologous platelets for the ophthalmologic treatment of macular holes

et al. 1999

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“…With the exception of cerebellar granule cells in the external granular layer, dividing neuronal progenitor cells are devoid of TGF‐β immunoreactivities suggesting that TGF‐β may mostly be involved in neuronal differentiation rather than cell division. This notion is also supported by the lack of TGF‐β immunostaining in the ventricular layer of the E12.3 mouse embryo [5] and both TGF‐β synthesis and immunostaining in the neuroepithelium of the E3.5 chick embryo [6]. Before neuronal perikarya in different areas of the CNS and in peripheral ganglia become immunoreactive for TGF‐β2 and ‐β3, very prominent staining can be seen in commissures of the hindbrain and spinal cord.…”

Section: Localization Of Tgf‐βs and Their Receptors In Neural Tissuesmentioning

confidence: 91%

“…TGF‐β is also an important regulator of neuronal differentiation. TGF‐β has been reported to stimulate neurite growth and regeneration of primary neurons in culture [6,29,30]. TGF‐β can also promote electrophysiological differentiation of neurons in terms of Ca 2+ activated K + channels [31,32] and long‐term facilitation in isolated Aplysia ganglia [33].…”

Section: In Vitro and In Vivo Studies Have Begun To Reveal Neural Funmentioning

confidence: 99%

Functions of transforming growth factor‐β isoforms in the nervous system

Unsicker

Strelau

2000

European Journal of Biochemistry

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This review briefly describes the cellular distribution and documented roles of the transforming growth factor (TGF)-b isoforms TGF-b2 and -b3 in the central and peripheral nervous system. TGF-b2 and -b3 are coexpressed in developing radial glial and mature astroglial and Schwann cells, as well as in subpopulations of differentiated neurons, most prominently in cortical, hippocampal, and brainstem/spinal cord motor neurons. In vitro studies have suggested a number of potential, physiologically relevant functions for TGF-bs including regulation of astroglial cell proliferation, expression of adhesion molecules, survival promoting roles for neurons in combination with established neurotrophic factors, and differentiative actions on neurons.Keywords: TGF-b isoforms; CNS; peripheral nervous system; distribution, development; glial cell biology; neuronal functions. I N T R O D U C T I O NTransforming growth factor (TGF)-bs are among the most abundant and functionally versatile cytokines in the central and peripheral nervous system. The discovery of TGF-b expression in the nervous system is only 10-year-old, and the list of functions elucidated by in vitro and in vivo manipulations of neural cells and tissues is still growing. We know now that TGF-b2 and -b3 are the`neural' TGF-b isoforms which jointly occur in many types of glial and neuronal cells, while TGF-b1 is normally restricted to choroid plexus epithelial and meningeal cells, but can be strongly induced in many cell types in the brain following lesioning. This minireview outlines the most prominent localizations of TGF-b2 and -b3 in the nervous system and summarizes the key functions documented so far. Roles of TGF-bs in neurodegenerative diseases and ischemic injury have not been included, as these issues have been recently covered by several excellent reviews [1,2]. L O C A L I Z A T I O N O F T G F -b S A N D T H E I R R E C E P T O R S I N N E U R A L T I S S U E SImmunohistochemical and in situ hybridization studies have revealed a widespread distribution of TGF-b2 and -b3 as well as their cognate serine/threonine kinase receptor TbRII in the developing and adult CNS and peripheral nervous system (reviewed in [3,4]).In the mouse embryonic nervous system, TGF-b2 and -b3 immunoreactivities can be detected along peripheral nerve trunks, CNS radial glial cells and along developing axon tracts as early as E12.5 [5]. At this time, cell bodies of neurons are still devoid of immunoreactivities suggesting that the strong staining of CNS and peripheral axonal tracts may result from immunostaining of glial or mesenchymal cells, respectively, rather than axonal staining. Central and peripheral neurons become TGF-b2 and -b3 immunoreactivities at about E15. With the exception of cerebellar granule cells in the external granular layer, dividing neuronal progenitor cells are devoid of TGF-b immunoreactivities suggesting that TGF-b may mostly be involved in neuronal differentiation rather than cell division. This notion is also supported by the lack of TGF-b immunostaini...

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Expression, localization, and function of transforming growth factor-?s in embryonic chick spinal cord, hindbrain, and dorsal root ganglia

Cited by 56 publications

References 56 publications

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Transforming growth factor-β induces cellular injury in experimental diabetic neuropathy

Preparation of autologous platelets for the ophthalmologic treatment of macular holes

Functions of transforming growth factor‐β isoforms in the nervous system

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