Metabolic Orchestration Of Epidermal Stem Cells And Adipocytes Promotes Healing In Obesity Wound
Ji LIN1, Xiao-ning GAO2.
1Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, China, 2Department of Hematology, Chinese PLA General Hospital, Beijing, China.
BACKGROUND: Wound healing is a world-wide health problem and the prominent obesity has made it profoundly difficult, for the unclear mechanism of obesity-impeded healing. As epidermal stem cells (EpiSCs) and adipocytes are vital elements in the structural, metabolic and healing process of skin, we hypothesize that the potent associations between them and the subsequent intervention may influence healing prognosis in the obesity. METHODS: A model of high fat diet-induced obesity using Sprague-Dawley rats was established, including groups of sham-injury (Sham), injury without cell transplantation (Injury), and injury plus EpiSCs transplantation, then a 6-mm diameter full-thickness excision was developed on the dorsal skin. 1×10^5 epidermal basal stem cells isolated from neonatal mice skin and suspended in 30 μl 1×PBS were injected subcutaneously into each wound in EpiSCs rats, as equivalent 1×PBS was injected similarly in Sham and Injury rats. Skin wounds and peripheral blood samples were harvested after injury, and subjected to histological investigations and colorimetric detections. RESULTS: At 1, 3 and 7 days after injury, significantly reduced scar, improved contraction, promoted re-epithelialization, repopulated perilipin A-positive adipocytes, and orderly increased collagen deposition in the wound bed were found in EpiSCs rats (P<0.05, vs Injury). Meanwhile, a down-and-up fluctuation of serum FABP5 and FABP4, two fatty acid binding protein subtypes secreted by epidermal cells and adipocytes respectively, was identified in EpiSCs rats at 1 and 3 days after injury, as serum FABP5:FABP4 ratios in EpiSCs rats were higher at 7 and 14 days after injury (P<0.05, vs Sham or Injury). Moreover, related alterations of metabolic markers such as serum lactate, pyruvate, lactate:pyruvate ratios, NAD+, NADH, NAD+:NADH ratios, insulin, triglycerides and total cholesterol, as well as immunohistochemical expressions of FABP5 and FABP4 in the wounds were identified. CONCLUSIONS: EpiSCs interact with adipocytes and evoke subsequent rehabilitation in obesity wound, indicating an underlying metabolic perspective for therapy.
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