PI3K/AKT pathway promotes keloid fibroblasts proliferation by enhancing glycolysis under hypoxia.
Our previous study demonstrated altered glucose metabolism and enhanced phosphorylation of the PI3K/AKT pathway in keloid fibroblasts (KFb) under hypoxic conditions. However, whether the PI3K/AKT pathway influences KFb cell function by regulating glucose metabolism under hypoxic conditions remains u...
| Published in: | Wound Repair & Regeneration Vol. 31; no. 2; pp. 139 - 156 |
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| Main Authors: | , , , , , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
Mar/Apr2023
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=162397489&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 162397489 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10671927 DPV jtl: Wound Repair & Regeneration issn: 10671927 maglogo: Y pubinfo: dt: Mar/Apr2023 vid: 31 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 162397489 161199057 162397489 162397489 10.1111/wrr.13067 162397489 ppf: 139 ppct: 17 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: PI3K/AKT pathway promotes keloid fibroblasts proliferation by enhancing glycolysis under hypoxia. aug: au: Wang, Qifei Yang, Xin Ma, Jianxun Xie, Xiang Sun, Yimou Chang, Xu Bi, Hongsen Xue, Hongyu Qin, Zelian affil: Department of Plastic Surgery, Peking University Third Hospital, Beijing, China sug: subj: Signal Transduction Keloid Drug Therapy Fibroblasts Cell Proliferation Glycolysis Anoxia Transcription Factors Reactive Oxygen Species Wound Healing Funding Source Phosphotransferases Keloid Proteins Analysis Factor Analysis Apoptosis Human Male Female Adolescence Young Adult Adult Middle Age Data Analysis Software Descriptive Statistics Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: Our previous study demonstrated altered glucose metabolism and enhanced phosphorylation of the PI3K/AKT pathway in keloid fibroblasts (KFb) under hypoxic conditions. However, whether the PI3K/AKT pathway influences KFb cell function by regulating glucose metabolism under hypoxic conditions remains unclear. Here, we show that when PI3K/AKT pathway was inactivated with LY294002, the protein expression of glycolytic enzymes decreased, while the amount of mitochondria and mitochondrial membrane potential increased. The key parameters of extracellular acidification rate markedly diminished, and those of oxygen consumption rate significantly increased after inhibition of the PI3K/AKT pathway. When the PI3K/AKT pathway was suppressed, the levels of reactive oxygen species (ROS) and mitochondrial ROS (mitoROS) were significantly increased. Meanwhile, cell proliferation, migration and invasion were inhibited, and apoptosis was increased when the PI3K/AKT pathway was blocked. Additionally, cell proliferation was compromised when KFb were treated with both SC79 (an activator of the PI3K/AKT pathway) and 2‐deoxy‐d‐glucose (an inhibitor of glycolysis), compared with the SC79 group. Moreover, a positive feedback mechanism was demonstrated between the PI3K/AKT pathway and hypoxia‐inducible factor‐1α (HIF‐1α). Our data collectively demonstrated that the PI3K/AKT pathway promotes proliferation and inhibits apoptosis in KFb under hypoxia by regulating glycolysis, indicating that the PI3K/AKT signalling pathway could be a therapeutic target for keloids. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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