Inhibition of glycogen synthase kinase 3 increased subventricular zone stem cells proliferation

Pachenari, Narges; Kiani, Sahar; Javan, Mohammad

doi:10.1016/j.biopha.2017.07.043

Cited by 18 publications

(14 citation statements)

References 51 publications

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“…In the case of an inhibitor of GSK-3β (CHIR-99021), no effect on proliferation after 48-h treatment was found. Similar results on the use of CHIR-99021 inhibitor were reported by [ 19 ]; GSK-3β inhibition promotes proliferation and neuronal differentiation of human-induced pluripotent stem cell-derived neural progenitors [ 20 ]. On the other hand, induction of apoptosis in pancreatic cancer cells was observed after application of GSK-3β (CHIR-99021) kinase inhibitor [ 21 ].…”

Section: Discussionsupporting

confidence: 82%

Treatment of melanoma with selected inhibitors of signaling kinases effectively reduces proliferation and induces expression of cell cycle inhibitors

2017

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Cancer treatment often tends to involve direct targeting enzymes essential for the growth and proliferation of cancer cells. The aim of this study was the recognition of the possible role of selected protein kinases: PI3K, ERK1/2, and mTOR in cell proliferation and cell cycle in malignant melanoma. We investigated the role of protein kinase inhibitors: U0126 (ERK1/2), LY294002 (PI3K), rapamycin (mTOR), everolimus (mTOR), GDC-0879 (B-RAF), and CHIR-99021 (GSK3beta) in cell proliferation and expression of crucial regulatory cell cycle proteins in human melanoma cells: WM793 (VGP) and Lu1205 (metastatic). They were used either individually or in various combinations. The study on the effect of signaling kinases inhibitors on proliferation—BrdU ELISA test after 48–72 h. Their effect on the expression of cell cycle regulatory proteins: cyclin D1 and D3, cyclin-dependent kinase CDK4 and CDK6, and cell cycle inhibitors: p16, p21, and p27, was studied at the protein level (western blot). Treatment of melanoma cells with protein kinase inhibitors led to significantly decreased cell proliferation except the use of a GSK-3β kinase inhibitors—CHIR-99021. The significant decrease in the expression of selected cyclins and cyclin-dependent kinases (CDKs) with parallel increase in the expression of some of cyclin-dependent kinases inhibitors and in consequence meaningful reduction in melanoma cell proliferation by the combinations of inhibitors of signaling kinases clearly showed the crucial role of AKT, ERK 1/2, and mTOR signal transduction in melanoma progression. The results unanimously indicate those pathways as an important target for treatment of melanoma.

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Section: Discussionsupporting

confidence: 82%

Treatment of melanoma with selected inhibitors of signaling kinases effectively reduces proliferation and induces expression of cell cycle inhibitors

2017

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“…In mice, pNSCs can be derived from implantation embryos (5.5–7.5 days postcoitum; Hitoshi et al, ) and from the periventricular region in the adult brain (Pachenari, Kiani, & Javan, ). These mouse pNSCs were also LIF‐responsive and efficiently differentiated into neurons and glial cells.…”

Section: Discussionmentioning

confidence: 99%

Derivation of primitive neural stem cells from human‐induced pluripotent stem cells

Shin

Seo

Choi

et al. 2019

J of Comparative Neurology

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Human-induced pluripotent stem cells (hiPSCs) have facilitated studies on organ development and differentiation into specific lineages in in vitro systems. Although numerous studies have focused on cellular differentiation into neural lineage using hPSCs, most studies have initially evaluated embryoid body (EB) formation, eventually yielding terminally differentiated neurons with limited proliferation potential. This study aimed to establish human primitive neural stem cells (pNSCs) from exogenefree hiPSCs without EB formation. To derive pNSCs, we optimized N2B27 neural differentiation medium through supplementation of two inhibitors, CHIR99021 (GSK-3 inhibitor) and PD0325901 (MEK inhibitor), and growth factors including basic fibroblast growth factor (bFGF) and human leukemia inhibitory factor (hLIF). Consequently, pNSCs were efficiently derived and cultured over a long term. pNSCs displayed differentiation potential into neurons, astrocytes, and oligodendrocytes.These early NSC types potentially promote the clinical application of hiPSCs to cure human neurological disorders. K E Y W O R D S differentiation, human-induced pluripotent stem cells, neural lineage, primitive neural stem cells

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“…ERK signaling negatively regulates L-Maf, an important factor needed to promote the differentiation of lens cells from the neural retina [53]. GSK-3 plays an important role in neural and retinal development [54,55] and is also involved with a variety of other signaling pathways (Wnt, hedgehog, insulin and notch) [56][57][58][59]. Inhibited by Akt during non-canonical signaling, Marchena et al also found that inhibition of GSK-3 by treatment with small molecule inhibitors led to retinal cell neuroprotection in a retinitis pigmentosa model [60].…”

Section: Tgf-β/bmp Signaling: Neural and Retinal Developmentmentioning

confidence: 99%

The Role of Small Molecules and Their Effect on the Molecular Mechanisms of Early Retinal Organoid Development

Wagstaff

Berzal

Boon

et al. 2021

IJMS

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Early in vivo embryonic retinal development is a well-documented and evolutionary conserved process. The specification towards eye development is temporally controlled by consecutive activation or inhibition of multiple key signaling pathways, such as the Wnt and hedgehog signaling pathways. Recently, with the use of retinal organoids, researchers aim to manipulate these pathways to achieve better human representative models for retinal development and disease. To achieve this, a plethora of different small molecules and signaling factors have been used at various time points and concentrations in retinal organoid differentiations, with varying success. Additions differ from protocol to protocol, but their usefulness or efficiency has not yet been systematically reviewed. Interestingly, many of these small molecules affect the same and/or multiple pathways, leading to reduced reproducibility and high variability between studies. In this review, we make an inventory of the key signaling pathways involved in early retinogenesis and their effect on the development of the early retina in vitro. Further, we provide a comprehensive overview of the small molecules and signaling factors that are added to retinal organoid differentiation protocols, documenting the molecular and functional effects of these additions. Lastly, we comparatively evaluate several of these factors using our established retinal organoid methodology.

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Inhibition of glycogen synthase kinase 3 increased subventricular zone stem cells proliferation

Cited by 18 publications

References 51 publications

Treatment of melanoma with selected inhibitors of signaling kinases effectively reduces proliferation and induces expression of cell cycle inhibitors

Treatment of melanoma with selected inhibitors of signaling kinases effectively reduces proliferation and induces expression of cell cycle inhibitors

Derivation of primitive neural stem cells from human‐induced pluripotent stem cells

The Role of Small Molecules and Their Effect on the Molecular Mechanisms of Early Retinal Organoid Development

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