Overexpression Of Lncrna Lethe Enhances Diabetic Wound Healing
Junwang Xu, Junyi Hu, Carlos Zgheib, Kenneth Liechty.
University of Colorado, Aurora, CO, USA.
Background: Impaired diabetic wound healing is associated with abnormal long non-coding RNA Lethe and chronic inflammation. We have previously shown that lncRNA Lethe is down-regulated in diabetic wounds and is involved in the regulation of Reactive oxygen species (ROS) production through modulation of NOX2 gene expression, indicating a potential role for Lethe in the pathogenesis of diabetic wounds. We hypothesized that overexpression of Lethe would reduce NOX2 expression and ROS production and enhance the wound-healing process. Methods: Db/Db diabetic mice and Db/+ non-diabetic mice were wounded with an 8-mm punch biopsy and the wounds treated with a lentiviral vector containing either the green fluorescent protein (GFP) or Lethe transgene. Computerized planimetry was used to measure wound size daily. Gain function of Lethe in RAW macrophage was achieved by transfection. Real-time PCR was applied to measure genes expression. Results: Overexpression of Lethe resulted in a significant increase in the rate of diabetic wound healing, (71% vs 99% in GFP-treated wounds at day 8 after injury; P < 0.02), and also improved the early phase of non-diabetic wound healing. Lethe overexpression resulted in significantly decreased NOX2 and pro-inflammatory cytokines including TNF-α, IL6 and MIP2, and ROS production in RAW macrophage. Discussion: The relative level of lncRNA Lethe in the wound plays a key role in the wound healing response. Alterations in the wound level of Lethe by overexpression, enhance healing by potentially decreasing ROS production and inflammatory cytokines in diabetic wounds.
Back to 2019 Abstracts