Open AccessHypoxia Regulates mTORC1-Mediated Keratinocyte Motility and Migration via the AMPK Pathway
Author(s) -
Tiantian Yan,
Junhui Zhang,
Di Tang,
Xingyue Zhang,
Xupin Jiang,
Liping Zhao,
Qiong Zhang,
Dongxia Zhang,
Yuesheng Huang
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0169155
Subject(s) - mtorc1 , microbiology and biotechnology , ampk , downregulation and upregulation , hypoxia (environmental) , motility , keratinocyte , hacat , wound healing , cell migration , biology , chemistry , cell , signal transduction , cell culture , phosphorylation , immunology , protein kinase a , pi3k/akt/mtor pathway , biochemistry , genetics , organic chemistry , oxygen , gene
Keratinocyte migration, the initial event and rate-limiting step in wound healing, plays a vital role in restoration of the intact skin barrier, also known as re-epithelialization. After acute tissue injury, hypoxic microenvironment gradually develops and acts as an early stimulus to initiate the healing process. Although we have previously found that hypoxia induces keratinocyte migration, the underlying mechanism remains unknown. Here, we first observed that hypoxia increased mTORC1 activity. Recombinant lentivirus vector and Rapamycin were used for silencing mTORC1 in HaCaT cells and primary mouse keratinocytes (MKs). Using cell migration assay and a Zeiss chamber equipped with imaging system, we also demonstrated that mTORC1 downregulation reversed hypoxia-induced keratinocyte motility and lateral migration. Importantly, hypoxia-activated mTORC1 was accompanied by the AMPK downregulation, and we found that the AMPK pathway activators Metformin (Met) and 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) decreased the mTORC1 activity, cell motility and lateral migration. Thus, our results suggest that hypoxia regulates mTORC1-mediated keratinocyte motility and migration via the AMPK pathway.