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.

瘢痕loid表现出代谢重编程，包括增强的糖酵解和减弱的氧化磷酸化。缺氧在哺乳动物细胞中诱导一系列保护性反应。然而，在缺氧条件下瘢痕fi成纤维细胞的代谢表型仍有待阐明。本研究旨在调查缺氧条件下瘢痕loid成纤维细胞（KFB）中的糖酵解活性，线粒体功能和形态，以及HIF1α和PI3K / AKT信号通路。我们的结果表明，缺氧促进了KFB的增殖，迁移侵袭和胶原蛋白合成，并抑制了其凋亡。在常氧下，KFB中的mRNA水平，糖酵解酶的蛋白表达和酶活性高于正​​常皮肤成纤维细胞（NFB）。此外，缺氧显着上调了KFB中的糖酵解。在常氧条件下，在KFB中检测到线粒体复合物活性降低和线粒体异常，缺氧加剧了损伤。细胞内代谢谱分析表明，低氧增加了糖酵解参数，除了糖酵解储备，但抑制了线粒体功能的关键参数（H除外）⁺泄漏。在3％氧气的情况下，HIF1α的蛋白质水平和PI3K / AKT信号通路的磷酸化水平上调。响应缺氧，观察到增强的总活性氧（ROS），线粒体ROS（mitoROS）和KFB的抗氧化活性。另外，自噬是由缺氧引起的。我们的数据共同证明缺氧条件下增强的糖酵解作用和线粒体功能减弱，表明缺氧调节的糖代谢改变可能是瘢痕loid的治疗靶点。