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• W3128307527 abstract "Blocking the mevalonate pathway for cholesterol reduction by using statin may have adverse effects including statin-induced colitis. Moreover, one of the predisposing factors for colitis is an imbalanced CD4+ T cell, which can be observed on the complete deletion of HMG-CoA reductase (HMGCR), a target of statins. In this study, we inquired geranylgeranyl pyrophosphate (GGPP) is responsible for maintaining the T-cell homeostasis. Following dextran sulfate sodium (DSS)-induced colitis, simvastatin increased the severity of disease, while cotreatment with GGPP, but not with cholesterol, reversed the disease magnitude. GGPP ameliorated DSS-induced colitis by increasing Treg cells. GGPP amplified Treg differentiation through increased IL-2/STAT 5 signaling. GGPP prenylated Ras protein, a prerequisite for extracellular signal-regulated kinase (ERK) pathway activation, leading to increased IL-2 production. Higher simvastatin dose increased the severity of colitis. GGPP ameliorated simvastatin-increased colitis by increasing Treg cells. Treg cells, which have the capacity to suppress inflammatory T cells and were generated through IL-2/STAT5 signaling, increased IL-2 production through prenylation and activation of the Ras/ERK pathway." @default.
• W3128307527 created "2021-02-15" @default.
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• W3128307527 date "2021-02-25" @default.
• W3128307527 modified "2023-10-18" @default.
• W3128307527 title "Geranylgeranyl pyrophosphate amplifies T _reg differentiation via increased IL‐2 expression to ameliorate DSS‐induced colitis" @default.
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• W3128307527 doi "https://doi.org/10.1002/eji.202048991" @default.
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• W3128307527 hasPublicationYear "2021" @default.
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