Polyamine Regulator AMD1 Promotes Cell Migration in Epidermal Wound Healing

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Polyamine Regulator AMD1 Promotes Cell Migration in Epidermal Wound Healing
Title:
Polyamine Regulator AMD1 Promotes Cell Migration in Epidermal Wound Healing
Journal Title:
Journal of Investigative Dermatology
Publication Date:
01 June 2018
Citation:
Lim HK, Rahim AB, Leo VI, Das S, Lim TC, Uemura T, Igarashi K, Common J, Vardy LA. Polyamine Regulator AMD1 Promotes Cell Migration in Epidermal Wound Healing. J Invest Dermatol. 2018 Dec;138(12):2653-2665. doi: 10.1016/j.jid.2018.05.029. Epub 2018 Jun 12. PMID: 29906410.
Abstract:
Wound healing is a dynamic process involving gene-expression changes that drive re-epithelialization. Here, we describe an essential role for polyamine regulator AMD1 in driving cell migration at the wound edge. The polyamines, putrescine, spermidine, and spermine are small cationic molecules that play essential roles in many cellular processes. We demonstrate that AMD1 is rapidly upregulated following wounding in human skin biopsies. Knockdown of AMD1 with small hairpin RNAs causes a delay in cell migration that is rescued by the addition of spermine. We further show that spermine can promote cell migration in keratinocytes and in human ex vivo wounds, where it significantly increases epithelial tongue migration. Knockdown of AMD1 prevents the upregulation of urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor on wounding and results in a failure in actin cytoskeletal reorganization at the wound edge. We demonstrate that keratinocytes respond to wounding by modulating polyamine regulator AMD1 in order to regulate downstream gene expression and promote cell migration. This article highlights a previously unreported role for the regulation of polyamine levels and ratios in cellular behavior and fate.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This research is supported by core funding from: Institute of Medical Biology, Agency for Science, Technology and Research
Grant Reference no. :
Description:
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