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Hypoxia Decreases Wound Stability via Degradation of the Extracellular Matrix
Author(s) -
Caesar Christa,
Adesina Sherry,
Naylor Petrina Barnett,
WoodardGrice Alencia
Publication year - 2017
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.31.1_supplement.lb501
Subject(s) - extracellular matrix , wound healing , hypoxia (environmental) , matrix metalloproteinase , chemistry , microbiology and biotechnology , basement membrane , extracellular , andrology , immunology , biochemistry , biology , medicine , oxygen , organic chemistry
The extracellular matrix (ECM) plays a pivotal role in the healing and repair of wounds. While several studies have established that exposure to hypoxia significantly impairs wound healing, few studies have explored the effects of hypoxia on the extracellular matrix (ECM) and its impact on wound stability. This study aims to determine the underlying mechanism(s) by which hypoxia affects wound stability over a 72 hour time‐course. We utilized a 3D human EpiDerm TM wound model (MatTek©) and hypothesize that chronic hypoxia significantly decreases wound stability by promoting degeneration of the ECM. To assess oxygen‐dependent wound stability we exposed 3D Epiderm TM wounded samples to Normoxia (21% O 2 ) or Hypoxia (1% O 2 ) for 0, 48, or 72 hours. We then assessed wound closure and stability (confocal microscopy and H&E staining) and measured expression profiles of ECM and adhesion molecules (qRT‐PCR). Hypoxia significantly altered the stability of the wound as observed via immunohistochemistry. Specifically, the leading edge of the wound was observed to recede with 72 hours of hypoxia which resulted in delayed wound closure (~80% decrease in wound re‐epithelialization, n≥3 independent experiments). The re‐epithelializing layer of cells was also observed to peel off the basement membrane in the samples exposed to 72 hours of hypoxia. Furthermore, relative to the untreated control samples, hypoxia‐exposed samples had altered expression of multiple ECM proteins including several collagens (~40% decrease in Col 14A1, ~60% Col 1A, 2–3 independent experiments) and matrix metalloproteinases (MMPs) (~50% decrease in MMP 14, 2–3 independent experiments). Ultimately, these results confirm that chronic exposure to hypoxia impairs wound healing via degradation of the ECM.