The Function of FGFR1 Signalling in the Spinal Cord: Therapeutic Approaches Using FGFR1 Ligands after Spinal Cord Injury

Haenzi, Barbara; Moon, Lawrence

doi:10.1155/2017/2740768

Cited by 17 publications

(13 citation statements)

References 101 publications

(101 reference statements)

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“…For exploration of possible mechanism underlying astrocytes-mediated inflammation after infrasound exposure, we focused on FGF2/FGFR1 pathway due to its important role in neuroinflammation. FGFR1, a tumorigenic receptor tyrosine kinase, plays an important role in some physiological processes and progression of cancer ( Woodbury and Ikezu, 2014 ; Haenzi and Moon, 2017 ; Tang C. et al, 2017 ). In some conditions, FGFR1 signaling can be stimulated by FGF2, which can lead to dimerization and dephosphorylation of FGFR1, exhibiting corresponding actions, not only including cell proliferation, cell growth, anti-apoptosis, but also anti-inflammation ( Yoshimura et al, 2001 ; Zittermann and Issekutz, 2006 ; Sun et al, 2017 ; Tang M.M.…”

Section: Discussionmentioning

confidence: 99%

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

Shi

Xiao

et al. 2018

Front. Neurosci.

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Infrasound, a kind of ambient noise, can cause severe disorders to various human organs, specially to central nervous system (CNS). Our previous studies have shown that infrasound-induced CNS injury was closely related with astrocytes activation and astrocytes-mediated neuroinflammation, but the underlying molecular mechanisms are still largely unclear. FGF2/FGFR1 (Fibroblast growth factor 2/Fibroblast growth factor receptor 1) pathway was reported to play an important role in anti-inflammation in CNS disorders. To further study the possible roles of FGF2/FGFR1 pathway in infrasound-induced CNS injury, here we exposed Sprague-Dawley rats or cultured astrocytes to 16 Hz, 150 dB infrasound, and explored the effects of FGF2 on infrasound-induced astrocytes activation and neuroinflammation. Western blotting, immunofluorescence and liquid chip method were used in this experiment. Our results showed that after 3- or 7-day exposure (2 h/day) of rats as well as 2 h exposure of cultured astrocytes to 16 Hz, 150 dB infrasound, astrocyte-expressed FGFR1 was downregulated in vivo and in vitro. FGF2 pretreatment not only inhibited infrasound-induced astrocyte activation in rat hippocampal CA1 region, but also reduced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-18, IL-6, and IFN-γ in vitro and in vivo. However, FGF2 significantly upregulated the expression of FGFR1. Furthermore, we showed that FGF2 could attenuate IκBα phosphorylation, NF-κB p65 translocation, pro-inflammatory cytokines levels, and neuronal loss in the CA1 region induced by infrasound. On the contrary, PD173074, a special antagonist of FGFR1, could reverse the effects above in vitro and in vivo. Taken together, our findings showed that FGF2/FGFR1 pathway may exert inhibitive effects on astrocyte-mediated neuroinflammation in vitro and in vivo after infrasound exposure.

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Section: Discussionmentioning

confidence: 99%

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

Shi

Xiao

et al. 2018

Front. Neurosci.

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“…At present, the research on aFGF is mostly focused on promoting the growth and differentiation of neurons and neurotrophic effects, but its role in ER stress-induced apoptosis is still unknown (Garré et al, 2010;Kuo et al, 2011). Moreover, as a macromolecular protein, it is easy to decompose in the body and has a short half-life, so a carrier is needed to solve this problem (Zakrzewska et al, 2008;Haenzi and Moon, 2017).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Response Element-Directed Expression of aFGF in Neural Stem Cells Promotes the Recovery of Spinal Cord Injury and Attenuates SCI-Induced Apoptosis

Ying

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Reducing neuronal death after spinal cord injury (SCI) is considered to be an important strategy for the renovation of SCI. Studies have shown that, as an important regulator of the development and maintenance of neural structure, acidic fibroblast growth factor (aFGF) has the role of tissue protection and is considered to be an effective drug for the treatment of SCI. Neural stem cells (NSCs) are rendered with the remarkable characteristics to self-replace and differentiate into a variety of cells, so it is promising to be used in cell transplantation therapy. Based on the facts above, our main aim of this research is to explore the role of NSCs expressing aFGF meditated by five hypoxia-responsive elements (5HRE) in the treatment of SCI by constructing AAV–5HRE–aFGF–NSCs and transplanting it into the area of SCI. Our research results showed that AAV–5HRE–aFGF–NSCs can effectively restore the motor function of rats with SCI. This was accomplished by inhibiting the expression of caspase 12/caspase 3 pathway, EIF2α–CHOP pathway, and GRP78 protein to inhibit apoptosis.

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“…In spinal cord injuries, functional recovery is attributed to FGF-mediated promotion of neuronal survival [ 52 – 54 ], reduction of glial reactivity [ 14 ], and stimulation of angiogenesis [ 55 ], which results in a reduction in the lesion volume [ 56 ]. FGF2 is also capable of stimulating synaptic plasticity [ 57 – 59 ].…”

Section: Discussionmentioning

confidence: 99%

Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)

Castro

Silva

Chiarotto

et al. 2020

Stem Cells International

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Dorsal root rhizotomy (DRZ) is currently considered an untreatable injury, resulting in the loss of sensitive function and usually leading to neuropathic pain. In this context, we recently proposed a new surgical approach to treat DRZ that uses platelet-rich plasma (PRP) gel to restore the spinal reflex. Success was correlated with the reentry of primary afferents into the spinal cord. Here, aiming to enhance previous results, cell therapy with bioengineered human embryonic stem cells (hESCs) to overexpress fibroblast growth factor 2 (FGF2) was combined with PRP. For these experiments, adult female rats were submitted to a unilateral rhizotomy of the lumbar spinal dorsal roots, which was followed by root repair with PRP gel with or without bioengineered hESCs. One week after DRZ, the spinal cords were processed to evaluate changes in the glial response (GFAP and Iba-1) and excitatory synaptic circuits (VGLUT1) by immunofluorescence. Eight weeks postsurgery, the lumbar intumescences were processed for analysis of the repaired microenvironment by transmission electron microscopy. Spinal reflex recovery was evaluated by the electronic Von Frey method for eight weeks. The transcript levels for human FGF2 were over 37-fold higher in the induced hESCs than in the noninduced and the wildtype counterparts. Altogether, the results indicate that the combination of hESCs with PRP gel promoted substantial and prominent axonal regeneration processes after DRZ. Thus, the repair of dorsal roots, if done appropriately, may be considered an approach to regain sensory-motor function after dorsal root axotomy.

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The Function of FGFR1 Signalling in the Spinal Cord: Therapeutic Approaches Using FGFR1 Ligands after Spinal Cord Injury

Cited by 17 publications

References 101 publications

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

Hypoxia Response Element-Directed Expression of aFGF in Neural Stem Cells Promotes the Recovery of Spinal Cord Injury and Attenuates SCI-Induced Apoptosis

Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs)

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