EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73042_C
WNT通路激活剂；抑制GSK3α和GSK3ß
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总览
CHIR98014是一种可逆的、细胞渗透性WNT通路激活剂，通过抑制糖原合成酶激酶3 （GSK3α和GSK3β）的两种同工酶，IC₅₀值分别为0.65和0.58 nM。与其他20种丝氨酸/苏氨酸或酪氨酸激酶相比，对GSK-3的选择性至少为500倍（Ring等人）。
分化
·在不存在VEGF的情况下，诱导人诱导性多能干细胞（iPSCs）分化为内皮祖细胞（Lian 等人）。
·在高磷培养中，促进大鼠间充质干细胞向成骨样方向分化，包括增强 BMP-2 表达、钙沉积和碱性磷酸酶活性（Guerrero 等人）。
代谢
·激活细胞中的糖原合成酶，降低血糖水平，并改善胰岛素抵抗大鼠和糖尿病 db/db 小鼠的葡萄糖处理能力（Ring 等人）。
疾病建模
·降低出生后大鼠大脑皮层和海马中的tau蛋白磷酸化水平。tau过度磷酸化与阿尔茨海默病中神经原纤维缠结的形成和轴突运输缺陷有关（Selenica 等人）。
细胞类型
内皮细胞，间充质干/祖细胞，中胚层，PSC衍生，成骨细胞，胰腺细胞，多能干细胞
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
分化
研究领域
疾病建模，神经科学，干细胞生物学
CAS 编号
252935-94-7
化学式
C₂₀H₁₇Cl₂N₉O₂
纯度
≥ 95 %
通路
WNT
靶点
GSK3
产品说明书及文档
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应用领域
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相关材料与文献
技术资料 (2)
文献 (4)
Efficient differentiation of human pluripotent stem cells to endothelial progenitors via small-molecule activation of WNT signaling. Stem cell reports 2014 NOV
Abstract
Human pluripotent stem cell (hPSC)-derived endothelial cells and their progenitors may provide the means for vascularization of tissue-engineered constructs and can serve as models to study vascular development and disease. Here, we report a method to efficiently produce endothelial cells from hPSCs via GSK3 inhibition and culture in defined media to direct hPSC differentiation to CD34(+)CD31(+) endothelial progenitors. Exogenous vascular endothelial growth factor (VEGF) treatment was dispensable, and endothelial progenitor differentiation was β-catenin dependent. Furthermore, by clonal analysis, we showed that CD34(+)CD31(+)CD117(+)TIE-2(+) endothelial progenitors were multipotent, capable of differentiating into calponin-expressing smooth muscle cells and CD31(+)CD144(+)vWF(+)I-CAM1(+) endothelial cells. These endothelial cells were capable of 20 population doublings, formed tube-like structures, imported acetylated low-density lipoprotein, and maintained a dynamic barrier function. This study provides a rapid and efficient method for production of hPSC-derived endothelial progenitors and endothelial cells and identifies WNT/β-catenin signaling as a primary regulator for generating vascular cells from hPSCs.
TGF-β prevents phosphate-induced osteogenesis through inhibition of BMP and Wnt/β-catenin pathways. PloS one 2014
Abstract
BACKGROUND: Transforming growth factor-β (TGF-β) is a key cytokine during differentiation of mesenchymal stem cells (MSC) into vascular smooth muscle cells (VSMC). High phosphate induces a phenotypic transformation of vascular smooth muscle cells (VSMC) into osteogenic-like cells. This study was aimed to evaluate signaling pathways involved during VSMC differentiation of MSC in presence or not of high phosphate. RESULTS: Our results showed that TGF-β induced nuclear translocation of Smad3 as well as the expression of vascular smooth muscle markers, such as smooth muscle alpha actin, SM22α, myocardin, and smooth muscle-myosin heavy chain. The addition of high phosphate to MSC promoted nuclear translocation of Smad1/5/8 and the activation of canonical Wnt/β-catenin in addition to an increase in BMP-2 expression, calcium deposition and alkaline phosphatase activity. The administration of TGF-β to MSC treated with high phosphate abolished all these effects by inhibiting canonical Wnt, BMP and TGF-β pathways. A similar outcome was observed in high phosphate-treated cells after the inhibition of canonical Wnt signaling with Dkk-1. Conversely, addition of both Wnt/β-catenin activators CHIR98014 and lithium chloride enhanced the effect of high phosphate on BMP-2, calcium deposition and alkaline phosphatase activity. CONCLUSIONS: Full VSMC differentiation induced by TGF-β may not be achieved when extracellular phosphate levels are high. Moreover, TGF-β prevents high phosphate-induced osteogenesis by decreasing the nuclear translocation of Smad 1/5/8 and avoiding the activation of Wnt/β-catenin pathway.
Efficacy of small-molecule glycogen synthase kinase-3 inhibitors in the postnatal rat model of tau hyperphosphorylation. British journal of pharmacology 2007
Abstract
BACKGROUND AND PURPOSE: Glycogen synthase kinase-3 (GSK-3) affects neuropathological events associated with Alzheimeŕs disease (AD) such as hyperphosphorylation of the protein, tau. GSK-3beta expression, enzyme activity and tau phosphorylated at AD-relevant epitopes are elevated in juvenile rodent brains. Here, we assess five GSK-3beta inhibitors and lithium in lowering phosphorylated tau (p-tau) and GSK-3beta enzyme activity levels in 12-day old postnatal rats. EXPERIMENTAL APPROACH: Brain levels of inhibitors following treatment in vivo were optimized based on pharmacokinetic data. At optimal doses, p-tau (Ser(396)) levels in brain tissue was measured by immunoblotting and correlated with GSK-3beta enzyme activities in the same tissues. Effects of GSK inhibitors on p-tau, GSK-3beta activities and cell death were measured in a human neuronal cell line (LUHMES). KEY RESULTS: Lithium and CHIR98014 reduced tau phosphorylation (Ser(396)) in the cortex and hippocampus of postnatal rats, while Alsterpaullone and SB216763 were effective only in hippocampus. AR-A014418 and Indirubin-3'-monoxime were ineffective in either brain region. Inhibition of p-tau in brain required several-fold higher levels of GSK inhibitors than the IC(50) values obtained in recombinant or cell-based GSK-3beta enzyme activity assays. The inhibitory effect on GSK-3beta activity ex vivo correlated with protection against cell death and decrease of p-tau- in LUHMES cells, using low microM inhibitor concentrations. CONCLUSIONS AND IMPLICATIONS: Selective small-molecule inhibitors of GSK-3 reduce tau phosphorylation in vivo. These findings corroborate earlier suggestions that GSK-3beta may be an attractive target for disease-modification in AD and related conditions where tau phosphorylation is believed to contribute to disease pathogenesis.
更多信息
| 种属 | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 252935-94-7 |
| Chemical Formula | C₂₀H₁₇Cl₂N₉O₂ |
| 纯度 | ≥ 95% |
| Target | GSK3 |
| Pathway | WNT |
