Effects of epigallocatechin-3-gallate on proliferation and differentiation of mouse cochlear neural stem cells: Involvement of PI3K/Akt signaling pathway

Zhang, Yubo; He, Qiang; Dong, Jinhui; Jia, Zhanwei; Hao, Fang; Shan, Chunguang

doi:10.1016/j.ejps.2016.03.017

Cited by 34 publications

(33 citation statements)

References 40 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, PI3K/AKT/mTOR signalling pathway was reported to be involved in the protective role of MSCs against cytokine-induced impairments 34 and the biological effects of EGCG in many conditions. [35][36][37] Consistently, our results also suggested that this signalling pathway was involved in MSC and EGCG combinational treatment…”

Section: Discussionsupporting

confidence: 87%

“…The therapeutic outcomes of MSCs with EGCG are likely to be context‐dependent, and careful evaluations of optimal doses and route of administration are needed to safely promote wound healing. Furthermore, PI3K/AKT/mTOR signalling pathway was reported to be involved in the protective role of MSCs against cytokine‐induced impairments and the biological effects of EGCG in many conditions . Consistently, our results also suggested that this signalling pathway was involved in MSC and EGCG combinational treatment (Figure ).…”

Section: Discussionsupporting

confidence: 87%

See 1 more Smart Citation

Epigallocatechin‐3‐gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing

Shi

et al. 2016

Clin Exp Pharma Physio

View full text Add to dashboard Cite

In non-healing wounds, mesenchymal stem cell (MSC)-based therapies have the potential to activate a series of coordinated cellular processes, including angiogenesis, inflammation, cell migration, proliferation and epidermal terminal differentiation. As pro-inflammatory reactions play indispensable roles in initiating wound repair, sustained and prolonged inflammation exhibit detrimental effects on skin wound closure. We investigated the feasibility of using an antioxidant agent epigallocatechin-3-gallate (EGCG), along with MSCs, to improve wound repair through their immunomodulatory actions. In a rat model of wound healing, a single dose of EGCG at 10 mg/kg increased the efficiency of MSC-induced skin wound closure. Twenty days after the wound induction, MSC treatment significantly enhanced the epidermal thickness, which was further increased by EGCG administration. Consistently, the highest extent of growth factors upregulation for neovascularization induction was seen in the animals treated by both MSCs and EGCG, associated with a potent anti-scarring effect throughout the healing process. Finally, expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6, in the wound area were reduced by MSCs, and this reduction was further potentiated by EGCG co-administration. EGCG, together with MSCs, can promote skin wound healing likely through their combinational effects in modulating chronic inflammation.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 87%

Epigallocatechin‐3‐gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing

Shi

et al. 2016

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…However, in-depth studies are needed to fully understand how flavone derivatives regulate astrocyte function and promote astrocytogenesis especially in NSC by PD98059, compound 2, and 3. Like our results, flavonoids have been known to regulate NSC fate [47,48]. It has been known that epigallocatechin-3-gallate induces proliferation and promotes neurogenesis of mouse cochlear NSCs [47].…”

Section: The 3 -Methoxy Group (Methoxy Group At R 2 Position) and Nonsupporting

confidence: 87%

“…Like our results, flavonoids have been known to regulate NSC fate [47,48]. It has been known that epigallocatechin-3-gallate induces proliferation and promotes neurogenesis of mouse cochlear NSCs [47]. However, in-depth studies are needed to fully understand how flavonoids and flavone derivatives can regulate NSC fate.…”

Section: The 3 -Methoxy Group (Methoxy Group At R 2 Position) and Nonsupporting

confidence: 77%

Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives

et al. 2019

View full text Add to dashboard Cite

Neural stem cells (NSCs) differentiate into multiple cell types, including neurons, astrocytes, and oligodendrocytes, and provide an excellent platform to screen drugs against neurodegenerative diseases. Flavonoids exert a wide range of biological functions on several cell types and affect the fate of NSCs. In the present study, we investigated whether the structure-activity relationships of flavone derivatives influence NSC differentiation. As previously reported, we observed that PD98059 (2′-amino-3′-methoxy-flavone), compound 2 (3′-methoxy-flavone) induced astrocytogenesis. In the present study, we showed that compound 3 (2′-hydroxy-3′-methoxy-flavone), containing a 3′-methoxy group, and a non-bulky group at C2′ and C4′, induced astrocytogenesis through JAK-STAT3 signaling pathway. However, compound 1 and 7–12 without the methoxy group did not show such effects. Interestingly, the compounds 4 (2′,3′-dimethoxyflavone), 5 (2′-N-phenylacetamido-3′-methoxy-flavone), and 6 (3′,4′-dimethoxyflavone) containing 3′-methoxy could not promote astrocytic differentiation, suggesting that both the methoxy groups at C3′ and non-bulky group at C2′ and C4′ are required for the induction of astrocytogenesis. Notably, compound 6 promoted neuronal differentiation, whereas its 4′-demethoxylated analog, compound 2, repressed neurogenesis, suggesting an essential role of the methoxy group at C4′ in neurogenesis. These findings revealed that subtle structural changes of flavone derivatives have pronounced effects on NSC differentiation and can guide to design and develop novel flavone chemicals targeting NSCs fate regulation.

show abstract

“…22 Such findings are of interest in light of recent work showing that EGCG acts through phosphoinositide 3-kinase (PI3K)/Akt signaling in cochlea neuronal stem cells to promote cell growth and neuron differentiation, which may be useful for the treatment of heari ng loss. 23 …”

Section: Discussionmentioning

confidence: 99%

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Jiang

Ray

Rybak³

et al. 2016

Otology &Amp; Neurotology

View full text Add to dashboard Cite

Rationale Oxidative stress plays a critical role in gentamicin-induced hair cell death. Prior work has implicated the cytoplasmic transcription factor STAT1 as a potential mediator of drug-induced ototoxicity, but role in aminoglycosides is largely unknown. This study investigated aminoglycosides-induced cell death, exploring contributions of reactive oxygen species and STAT1 pathway in injury and protection. Methods Neonatal murine organ of Corti explants from 2-3 day postnatal pups (n=96) were treated with gentamicin at (4 μΜ, 50 μΜ) for 4-72 hours, with/without protectants. Effects on STAT1 pathway and gentamicin-induced hair cell death were measured with 50 μΜ Epigallocatechin Gallate (EGCG, a STAT1 inhibitor) and all-trans retinoic acid (atRA, a STAT1 activator). Hair cell morphology was evaluated and hair cell loss was quantified with cytocochleograms. Mitochondrial membrane potential was assayed and superoxide generation and suppression was measured with dihydroethidium (DHE) staining. Results Co-administration of 50 μΜ EGCG conferred protection from 4 μΜ gentamicin toxicity (p < 0.001), whereas atRA potentiated gentamicin-induced hair cell death (p<.001). On immunohistochemistry, STAT1 phosphorylation at theserine 727 (Ser727) residues was increased at 72 hours with 4 μΜ gentamicin. With administration of 50 μΜ gentamicin, there was activation of STAT1 Tyr701 at 4 hours and STAT1 Ser727 at 16 hours. Gentamicin dissipated mitochondrial membrane potentials, and EGCG attenuated gentamicin-induced oxidative stress at 72 hours. Conclusion EGCG protected outer hair cells from gentamicin toxicity in a cochlear explant model, with the underlying mechanism involving both reactive oxygen species (ROS) suppression and STAT1 inhibition.

show abstract

Effects of epigallocatechin-3-gallate on proliferation and differentiation of mouse cochlear neural stem cells: Involvement of PI3K/Akt signaling pathway

Cited by 34 publications

References 40 publications

Epigallocatechin‐3‐gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing

Epigallocatechin‐3‐gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing

Functional Group-Dependent Induction of Astrocytogenesis and Neurogenesis by Flavone Derivatives

Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Contact Info

Product

Resources

About