下调和上调
mTORC1型
细胞生物学
细胞生长
过剩1
生物
发病机制
基因敲除
癌症研究
葡萄糖转运蛋白
信号转导
免疫学
内分泌学
生物化学
PI3K/AKT/mTOR通路
细胞凋亡
胰岛素
基因
作者
Wei Du,Zhao Song,Fan Gao,Mengyu Wei,Jiahui An,Keqi Jia,Fan Li,Lin Zhu,Jun Hao
摘要
Abstract Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Rab11 is conserved gene‐regulating vesicle traffic and reported to be involved in the pathogenesis of diabetes mellitus by affecting insulin sensitivity. We aimed to investigate the role of Rab11 in the pathogenesis of DPN. In this study, Rab11 expression decreased in the sciatic nerves of diabetic mice with impaired conduction function versus those of normal mice. In vitro experiment revealed interferon‐γ (IFN‐γ), not high glucose and interleukin 1β was the main factor to lead to Rab11 downregulation in RSC96 cells. Again, both Rab11 knockdown and IFN‐γ treatment caused cell viability inhibition and the decrease in BrdU‐positive cells. In contrast, overexpression of Rab11 reversed IFN‐γ‐reduced cell proliferation. Furthermore, mTORC1 not mTORC2 was proven to be suppressed by IFN‐γ treatment in RSC96 cells, indicated in decreased phospho‐p70S6K. Inhibition of the mTORC1 pathway resulted in Rab11 expression downregulation in RSC96 cells. Activation of the mTORC1 pathway effectively prevented IFN‐γ‐reduced Rab11 expression in RSC96 cells. Also, glucose transporter 1 (GLUT1) was found to be downregulated in RSC96 cells with Rab11 silence and overexpression of GLUT1 reversed Rab11 blocking‐caused proliferation inhibition. Taken together, our findings suggest that IFN‐γ decreases Rab11 expression via the inhibition of the mTORC1 signaling pathway, causing reduced cell proliferation in Schwann cells of DPN by GLUT1 downregulation.
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