Direct interaction of receptor tyrosine kinases, EphA4 and PDGFR&amp;beta;, plays an important role in the proliferation of neural stem cells

Chen, Qingfa; Sawada, Takahiro; Sakaguchi, Kazushige; Han, Fabin

doi:10.2147/jn.s139820

Cited by 5 publications

(8 citation statements)

References 55 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have found a direct interaction between EphA4 and PDGFRβ in NPCs. This result is consistent with a previous study showing a direct interaction between them in HEK293T cells after overexpression of EphA4 and PDGFRβ (Chen et al, 2017). In this report, EphA4 dominant-negative mutant showed a strong inhibitory effect on PDGF-BB treatment of BrdU + cells and Tuj1 + cells almost to the basal level; this is probably because EphA4 dominant-negative mutant inhibited both the PDGF-mediated and the ephrin-mediated signaling.…”

Section: Discussionsupporting

confidence: 93%

“…Further, we confirmed the overexpression of dominant-negative EphA4 mutant by immunoblotting and compared with the intrinsic EphA4 (p < 0.001; Figure 1H), and the expression level was consistent with the previous report (Sawada et al, 2010). These results together with our previous report (Chen et al, 2017) strongly suggested that EphA4 and PDGFRβ could bind to each other directly. The signals mediated by the crosstalk were then detected in mouse embryonic NPCs where both the receptors were expressed.…”

Section: Interaction Between Epha4 and Pdgfrβ In Mouse Embryonic Npcssupporting

confidence: 92%

“…Our previous study showed that EphA4 and fibroblast growth factor receptors (FGFRs) form a heterodimer, phosphorylate each other when stimulated by ligands, and their interaction promotes proliferation and neurogenesis of mouse embryonic NPCs via FGFR substrate 2α (FRS2α) and extracellular regulated protein kinases 1/2 (ERK1/2; Sawada et al, 2015). We also reported that EphA4 and platelet-derived growth factor receptor β (PDGFRβ) formed a heterodimer when they were co-expressed in HEK293T cells and human embryonic stem cell-derived NPCs (Chen et al, 2017). However, the functional role of this interaction on neurogenesis in AD-transgenic mice has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Interaction of EphA4 With PDGFRβ Regulates Proliferation and Neuronal Differentiation of Neural Progenitor Cells in vitro and Promotes Neurogenesis in vivo

Chen

Song

Liu

et al. 2020

Front. Aging Neurosci.

Self Cite

View full text Add to dashboard Cite

Neural progenitor cells (NPCs) have great potentials in cell replacement therapy for neurodegenerative diseases, such as Alzheimer's disease (AD), by promoting neurogenesis associated with hippocampal memory improvement. Ephrin receptors and angiogenic growth factor receptors have a marked impact on the proliferation and differentiation of NPCs. Although ephrin receptor A4 (EphA4) was shown to directly interact with platelet-derived growth factor receptor β (PDGFRβ), the functional effects of this interaction on neurogenesis in cultured NPCs and adult hippocampus have not yet been studied. Immunoprecipitation demonstrated that EphA4 directly interacted with PDGFRβ in NPCs under ligand stimulation. Ephrin-A1 and PDGF-platelet-derived growth factor BB (BB) significantly increased proliferation and neuronal differentiation of NPCs, which was further augmented by combined treatment of Ephrin-A1 and PDGF-BB. We also found that ligand-dependent proliferation and neuronal differentiation were inhibited by the dominant-negative EphA4 mutant or a PDGFR inhibitor. Most importantly, injection of ephrin-A1 and/or PDGF-BB promoted hippocampal NPC proliferation in the APP/PS1 mouse model of AD, indicating that direct interaction of EphA4 with PDGFRβ plays a functional role on neurogenesis in vivo. Finally, studies in NPCs showed that the EphA4/PDGFRβ/FGFR1/FRS2α complex formed by ligand stimulation is involved in neurogenesis via ERK signaling. The present findings provided a novel insight into the functional role of direct interaction of EphA4 and PDGFRβ in neurogenesis, implicating its potential use for treating neurodegenerative diseases.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Interaction Between Epha4 and Pdgfrβ In Mouse Embryonic Npcssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Interaction of EphA4 With PDGFRβ Regulates Proliferation and Neuronal Differentiation of Neural Progenitor Cells in vitro and Promotes Neurogenesis in vivo

Chen

Song

Liu

et al. 2020

Front. Aging Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous research showed that EphA4 and PDGFRs or EphA4 and FGFRs could form a heterodimer, trans-phosphorylating each other when overexpressed in 293T cells or after stimulation with their ligands (17,18). In the present study, a kinase-dependent interaction between EphA4 and VEGFR2 was found.…”

Section: Discussionsupporting

confidence: 69%

“…Previous research has shown that EphA4 and PDGF receptors (PDGFRs) form a heterodimer, trans-phosphorylating each other after stimulation with their ligands, and that their interaction promotes mouse embryonic neural precursor cell QINGFA CHEN 1* , JIA LIU 2* , TAKAHIRO SAWADA 3 , CHUANFEI WEI 1 , SHICHAO WU 1 and FABIN HAN 1 proliferation (17). It is therefore important to examine whether EphA4 and VEGFR2 form a heterocomplex and their role in NSPC differentiation.…”

Section: Introductionmentioning

confidence: 99%

Possible role of EphA4 and VEGFR2 interactions in neural stem and progenitor cell differentiation

et al. 2020

Self Cite

View full text Add to dashboard Cite

Neural stem and progenitor cells (NSPCs) are important pluripotent stem cells, which have potential applications for cell replacement therapy. Ephrin receptors (Ephs) and angiogenic growth factor receptors have a major impact on the proliferation and differentiation of NSPCs. Potential interactions between EphA4 and vascular endothelial growth factor (VEGF) receptor (VEGFR) 2, and their roles in NSPC differentiation in vitro remain unknown. In the present study, mouse embryonic NSPCs were treated with ephrin-A1 or VEGF165 alone as well as with combination treatment (ephrin-A1 + VEGF165). Immunoprecipitation and immunoblot assays demonstrated that wild-type EphA4, but not the EphA4 kinase-dead mutant, interacted with VEGFR2 when overexpressed in 293T cells. This interaction was inhibited by dominant-negative EphA4. The percentage of β-tubulin III (Tuj1) + , but not glial fibrillary acid protein (GFAP) + cells, was increased in the ephrin-A1 + VEGF165 combination group as compared to the VEGF165 alone group in mouse embryonic NSPCs. VEGF165-induced neuronal differentiation was potentiated by ephrin-A1 in NSPCs in vitro and ephrin-A1-or VEGF165-stimulated EphA4 and VEGFR2 interactions may mediate the signaling pathway.

show abstract

Fascia lata packing and tension suturing for symptomatic pseudomeningocele after recurrent cervical intradural tumour resection

Huang

Zhong

et al. 2021

Sci Rep

View full text Add to dashboard Cite

In recurrent posterior cervical intradural tumour resections, serious complications can be developed. The dural can become affected by inflammatory factors or removed during tumor resection; if cerebrospinal fluid (CSF) leakage cannot be stopped by duraplasty, artificial meninges or fascia repair, large pseudomeningocele can develop posteriorly within the soft tissue of the neck. When the pressure of the CSF cannot be maintained steadily, persistent clinical symptoms can occur, such as postural headache or central fever. Moreover, the skin can also be penetrated in a few patients even after extension of the drainage duration, lumbar cistern drainage or skin suturing, leading to the induction of life-threatening intra-cranial infections. Is there a simple and effective surgical method to address this scenario? The aim of this study was, therefore, to investigate the effectiveness of fascia lata packing and tension suturing in the treatment of symptomatic pseudomeningocele after recurrent posterior cervical intradural tumour resection. In our study, nine consecutive spinal surgery patients were recruited from January 2008 to January 2018. All pseudomeningoceles were combined with postural headache, central neurological fever or wound non-union. There were 3 cases of melanocytoma, 3 cases of nasopharyngeal carcinoma metastasis, 2 cases of breast cancer metastasis, and 1 case of spinal canal lymphadenoma. Standard patient demographics, diagnosis, post-operative symptoms, wound healing time, and the largest pre- and last follow-up pseudomeningocele area on axial MRI sections were recorded. All cases were followed-up successfully, from 12 to 24 months, with an average of 15.3 months. Our observations indicate that all wounds healed successfully. The wound union time was 20.7 days on average. After wound union, these patients became symptom free. The largest cerebrospinal fluid area on axial MRI sections improved significantly from 42.9 ± 5.01 cm2 at p re-operation to 6.6 ± 1.89 cm2 at 1 year post-operation (P < 0.05); Our data indicate that .the proposed procedure is simple, safe and effective. And more importantly, it allows rapid closure of any cerebrospinal fluid leakage pools.

show abstract

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells

Cited by 5 publications

References 55 publications

The Interaction of EphA4 With PDGFRβ Regulates Proliferation and Neuronal Differentiation of Neural Progenitor Cells in vitro and Promotes Neurogenesis in vivo

The Interaction of EphA4 With PDGFRβ Regulates Proliferation and Neuronal Differentiation of Neural Progenitor Cells in vitro and Promotes Neurogenesis in vivo

Possible role of EphA4 and VEGFR2 interactions in neural stem and progenitor cell differentiation

Fascia lata packing and tension suturing for symptomatic pseudomeningocele after recurrent cervical intradural tumour resection

Contact Info

Product

Resources

About