Effect of local application of transforming growth factor–β at the nerve repair site following chronic axotomy and denervation on the expression of regeneration-associated genes

2014 ◽  
Vol 121 (4) ◽  
pp. 859-874 ◽  
Author(s):  
Wale Sulaiman ◽  
Thomas D. Dreesen
Keyword(s):  
Growth Factor ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Functional Recovery ◽  
Transforming Growth Factor ◽  
Nerve Repair ◽  
Transforming Growth Factor Β ◽  
Distal Stump ◽  
Repair Site ◽  
Gene And Protein Expression

Object Although peripheral nerves can regenerate after traumatic injury, functional recovery is often suboptimal, especially after injuries to large nerve trunks such as the sciatic nerve or brachial plexus. Current research with animal models suggests that the lack of functional recovery resides in the lack of sufficient mature axons reaching their targets due to the loss of neurotrophic support by Schwann cells in the distal stump of injured nerves. This study was designed to investigate the effect of one-time application of transforming growth factor–β (TGF-β) at the repair site of chronically injured nerve. Methods The authors used the rat tibial nerve injury and repair model to investigate the effects of application of physiological concentrations of TGF-β plus forskolin or forskolin alone in vivo at the repair site on gene and protein expression and axon regeneration at 6 weeks after nerve repair. They used gene expression profiling and immunohistochemical analysis of indicative activated proteins in Schwann cells to evaluate the effects of treatments on the delayed repair. They also quantified the regenerated axons distal to the repair site by microscopy of paraffin sections. Results Both treatment with forskolin only and treatment with TGF-β plus forskolin resulted in increased numbers of axons regenerated compared with saline-only control. There was robust activation and proliferation of both Schwann cells and macrophages reminiscent of the processes during Wallerian degeneration. The treatment also induced upregulation of genes implicated in cellular activation and growth as detected by gene array. Conclusions Addition of TGF-β plus forskolin to the repair after chronic nerve injury improved axonal regeneration, probably via upregulation of required genes, expression of growth-associated protein, and reactivation of Schwann cells and macrophages. Further studies are required to better understand the mechanism of the positive effect of TGF-β treatment on old nerve injuries.

scholarly journals The Regulatory Effects of Transforming Growth Factor-β on Nerve Regeneration

2017 ◽  
Vol 26 (3) ◽  
pp. 381-394 ◽  
Author(s):  
Shiying Li ◽  
Xiaosong Gu ◽  
Sheng Yi
Keyword(s):  
Nervous System ◽  
Growth Factor ◽  
Nerve Injury ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Transforming Growth Factor Β ◽  
The Body ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Regulatory Effects

Transforming growth factor-β (TGF-β) belongs to a group of pleiotropic cytokines that are involved in a variety of biological processes, such as inflammation and immune reactions, cellular phenotype transition, extracellular matrix (ECM) deposition, and epithelial–mesenchymal transition. TGF-β is widely distributed throughout the body, including the nervous system. Following injury to the nervous system, TGF-β regulates the behavior of neurons and glial cells and thus mediates the regenerative process. In the current article, we reviewed the production, activation, as well as the signaling pathway of TGF-β. We also described altered expression patterns of TGF-β in the nervous system after nerve injury and the regulatory effects of TGF-β on nerve repair and regeneration in many aspects, including inflammation and immune response, phenotypic modulation of neural cells, neurite outgrowth, scar formation, and modulation of neurotrophic factors. The diverse biological actions of TGF-β suggest that it may become a potential therapeutic target for the treatment of nerve injury and regeneration.

scholarly journals The effects of resveratrol on the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells of women with endometriosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tahereh Arablou ◽  
Naheed Aryaeian ◽  
Sepideh Khodaverdi ◽  
Roya Kolahdouz-Mohammadi ◽  
Zahra Moradi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Antioxidant Properties ◽  
Transforming Growth Factor Β ◽  
Vascular Endothelial ◽  
Endometrial Stromal Cells ◽  
Gene And Protein Expression ◽  
Endothelial Growth Factor

AbstractResveratrol is a phytochemical with anti-angiogenic, anti-inflammatory, and antioxidant properties. The present study has evaluated the effect of resveratrol on the expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) and matrix metalloproteinase-9 (MMP-9) as factors related to endometriosis progression. Thirteen eutopic (EuESCs) and 8 ectopic (EESCs) endometrial stromal cells from women with endometriosis and 11 control endometrial stromal cells (CESCs) were treated with resveratrol (100 µM) for 6, 24 and 48 h. The gene and protein expression levels of VEGF, TGF-β, and MMP-9 were measured using real-time PCR and ELISA methods, respectively. Results showed that the basal gene and protein expression of VEGF and MMP-9 were higher in EESCs compared to EuESCs and CESCs (P < 0.01 to  < 0.001 and P < 0.05 to  < 0.01 respectively). Also, resveratrol treatment decreased the gene and protein expression of VEGF and MMP-9 in EuESCs, EESCs and CESCs (P < 0.05 to  < 0.01 and P < 0.05 to  < 0.01 respectively) and gene and protein expression of TGF-β in EESCs and EuESCs (P < 0.05 to  < 0.01). The effect of resveratrol in reduction of VEGF gene expression was statistically more noticeable in EESCs compared to EuESCs and CESCs (P < 0.05). According to the findings, resveratrol may ameliorate endometriosis progression through reducing the expression of VEGF, TGF-β, and MMP-9 in endometrial stromal cells (ESCs).

scholarly journals Glial Growth Factor/Neuregulin Inhibits Schwann Cell Myelination and Induces Demyelination

2001 ◽  
Vol 152 (6) ◽  
pp. 1289-1300 ◽  
Author(s):  
George Zanazzi ◽  
Steven Einheber ◽  
Richard Westreich ◽  
Melanie-Jane Hannocks ◽  
Debra Bedell-Hogan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Schwann Cell ◽  
Schwann Cells ◽  
Transforming Growth Factor ◽  
Significant Proportion ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Neuregulin 1 ◽  
Glial Growth Factor

During development, neuregulin-1 promotes Schwann cell proliferation and survival; its role in later events of Schwann cell differentiation, including myelination, is poorly understood. Accordingly, we have examined the effects of neuregulin-1 on myelination in neuron-Schwann cell cocultures. Glial growth factor (GGF), a neuregulin-1 isoform, significantly inhibited myelination by preventing axonal segregation and ensheathment. Basal lamina formation was not affected. Treatment of established myelinated cultures with GGF resulted in striking demyelination that frequently began at the paranodes and progressed to the internode. Demyelination was dose dependent and accompanied by dedifferentiation of Schwann cells to a promyelinating stage, as evidenced by reexpression of the transcription factor suppressed cAMP-inducible POU; a significant proportion of cells with extensive demyelination also proliferated. Two other Schwann cell mitogens, fibroblast growth factor-2 and transforming growth factor-β, inhibited myelination but did not cause demyelination, suggesting this effect is specific to the neuregulins. The neuregulin receptor proteins, erbB2 and erbB3, are expressed on ensheathing and myelinating Schwann cells and rapidly phosphorylated with GGF treatment. GGF treatment of myelinating cultures also induced phosphorylation of phosphatidylinositol 3-kinase, mitogen-activated protein kinase, and a 120-kD protein. These results suggest that neuronal mitogens, including the neuregulins, may inhibit myelination during development and that activation of mitogen signaling pathways may contribute to the initial demyelination and subsequent Schwann cell proliferation observed in various pathologic conditions.

ROLE OF CHRONIC SCHWANN CELL DENERVATION IN POOR FUNCTIONAL RECOVERY AFTER NERVE INJURIES AND EXPERIMENTAL STRATEGIES TO COMBAT IT

Neurosurgery ◽  
2009 ◽  
Vol 65 (suppl_4) ◽  
pp. A105-A114 ◽  
Author(s):  
Olawale A.R. Sulaiman ◽  
Tessa Gordon
Keyword(s):  
Schwann Cells ◽  
Functional Recovery ◽  
Axonal Regeneration ◽  
Transforming Growth Factor ◽  
Motor Units ◽  
Transforming Growth Factor Β ◽  
The Common ◽  
Distal Nerve ◽  
Experimental Strategies

Abstract OBJECTIVE To present our data about the role of chronic denervation (CD) of the distal nerve stumps as compared with muscle denervation atrophy and experimental strategies to promote better functional recovery. METHODS A rat model of nerve injury and repair was used. The common peroneal branch of the sciatic nerve was subjected to 0 to 24 weeks of CD before cross-suture with the tibial motoneurons. Our outcome measures included the numbers of motoneurons that regenerated their axons and the numbers that reinnervated muscle targets (motor units). To overcome the effects of CD, we used subcutaneous injection of FK506 and in vitro reactivation of Schwann cells that had been subjected to 24 weeks of CD with transforming growth factor β. RESULTS Numbers of regenerated motoneurons and reinnervated motor units decreased as a function of duration of CD. However, axons that regenerated through the distal nerve stumps reinnervated the muscle targets and even formed enlarged motor unit size regardless of the duration of CD. FK506 doubled the numbers of tibial motoneurons that regenerated their axons into the common peroneal nerve even after delayed repair. Reactivation of chronically denervated Schwann cells with transforming growth factor β significantly increased their capacity to support axonal regeneration. CONCLUSION CD of the distal nerve stumps is the primary factor that results in poor axonal regeneration and subsequently poor functional recovery. Acceleration of the rate of axonal regeneration and/or reactivation of Schwann cells of the distal nerve stumps are effective experimental strategies to promote axonal regeneration and functional recovery.

Perianale Fisteln bei CED: vom Mausmodell zur Klinik

2018 ◽  
Vol 75 (5) ◽  
pp. 287-294
Author(s):  
Michael Scharl
Keyword(s):  
Growth Factor ◽  
Morbus Crohn ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 13

Zusammenfassung. Fisteln stellen nach wie vor eine der wichtigsten Komplikationen bei Patienten mit Morbus Crohn dar. Bei mindestens einem Drittel aller Morbus Crohn Patienten treten im Laufe der Erkrankung Fisteln auf. Eine dauerhafte Heilung der Fistel wird jedoch, auch unter Ausschöpfung sämtlicher medikamentöser und chirurgischer Therapieoptionen, nur in rund einem Drittel dieser Patienten erreicht. Der genaue molekulare Mechanismus der Fistelentstehung ist bis heute nicht ganz klar. Aus histopathologischer Sichtweise stellen Fisteln eine röhrenartige Struktur dar, welche von flachen epithelartigen Zellen ausgekleidet ist. Als ursächlicher Entstehungsmechanismus wird dabei die sogenannte epitheliale-zu-mesenchymale Transition (EMT) angesehen und es kann eine starke Expression der Entzündungsmediatoren Tumor Nekrose Faktor, Interleukin-13 und Transforming Growth Factor β in den Fistelarealen nachgewiesen werden. Zusätzlich zu den bereits etablierten, medikamentösen Therapieoptionen, also Antibiotika, Immunmodulatoren und anti-TNF Antikörper, stellt insbesondere der Einsatz der mesenchymalen Stammzelltherapie einen erfolgversprechenden Therapieansatz für die Zukunft dar.

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