糖酵解
PI3K/AKT/mTOR通路
瘢痕疙瘩
线粒体
蛋白激酶B
氧化磷酸化
细胞生物学
线粒体ROS
缺氧(环境)
自噬
下调和上调
活性氧
化学
厌氧糖酵解
细胞凋亡
信号转导
生物化学
新陈代谢
生物
氧气
病理
医学
基因
有机化学
作者
Qifei Wang,Pu Wang,Zelian Qin,Xin Yang,Bailin Pan,Fangfei Nie,Hongsen Bi
出处
期刊:Redox biology
[Elsevier]
日期:2021-01-01
卷期号:38: 101815-101815
被引量:56
标识
DOI:10.1016/j.redox.2020.101815
摘要
Keloids exhibit metabolic reprogramming including enhanced glycolysis and attenuated oxidative phosphorylation. Hypoxia induces a series of protective responses in mammalian cells. However, the metabolic phenotype of keloid fibroblasts under hypoxic conditions remains to be elucidated. The present study aimed to investigate glycolytic activity, mitochondrial function and morphology, and the HIF1α and PI3K/AKT signaling pathways in keloid fibroblasts (KFB) under hypoxic conditions. Our results showed that hypoxia promoted proliferation, migration invasion and collagen synthesis and inhibited apoptosis in KFB. The mRNA levels, protein expressions and enzyme activities of glycolytic enzymes in KFB were higher than those in normal skin fibroblasts (NFB) under normoxia. Moreover, hypoxia remarkedly upregulated glycolysis in KFB. Decreased activities of mitochondrial complexes and abnormal mitochondria were detected in KFB under normoxic conditions and the damage was aggravated by hypoxia. An intracellular metabolic profile assay suggested hypoxia increased glycolytic parameters except glycolytic reserve but inhibited the key parameters of mitochondrial function apart from H+ leak. Protein levels of HIF1α and phosphorylation levels of the PI3K/AKT signaling pathway were upregulated in the context of 3% oxygen. Enhanced total reactive oxygen species (ROS), mitochondrial ROS (mitoROS) and antioxidant activities of KFB were observed in response to hypoxia. Additionally, autophagy was induced by hypoxia. Our data collectively demonstrated potentiated glycolysis and attenuated mitochondrial function under hypoxia, indicating that altered glucose metabolism regulated by hypoxia could be a therapeutic target for keloids.
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