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Epidermal growth factor receptor activation in an in vitro diabetes model
Author(s) -
Quan Krystle,
Hudson Laurie G
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.856.12
Subject(s) - glycation , tyrosine phosphorylation , wound healing , epidermal growth factor receptor , endocrinology , keratinocyte , receptor , medicine , receptor tyrosine kinase , diabetes mellitus , keratinocyte growth factor , epidermal growth factor , phosphorylation , cancer research , microbiology and biotechnology , chemistry , growth factor , biology , in vitro , immunology , biochemistry
Diabetes is the fifth leading cause of death in the United States and a major cause of morbidity. One of the more troubling complications in diabetes are non‐healing skin wounds, where high glucose levels and poor blood flow contribute to the formation of infected sores and ulcers. Hyperglycemia leads to the accumulation of advanced glycation end products, which can alter receptor functions. Because the epidermal growth factor receptor (EGFR) plays a crucial role in keratinocyte migration and wound reepithelialization, we tested the impact of high glucose on EGFR signaling in a human keratinocyte cell line. Basal EGFR tyrosine phosphorylation was decreased in cells following chronic exposure to high glucose (4.5 g/l) compared to cells maintained in normal glucose (1.0 g/l). Acute exposure of cells with high glucose diminished ligand‐stimulated EGFR tyrosine phosphorylation. This response was evident within 2‐4 hrs of high glucose treatment and became more pronounced with extended exposure. Similarly, downstream EGFR signaling, as detected by ERK phosphorylation, was decreased with time following high glucose treatment. These experiments demonstrate that high glucose interferes with EGF receptor function in keratinocytes with predicted impacts on cell migration and other EGFR‐dependent functions in wound reepithelialization. Funded by NIH award R01 GM079381.