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Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
MicroRNA-34a deficiency leads to impaired wound closure by augmented inflammation in mice
Na Zhao1, Guojian Wang1, Shuang Long1
1Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
Background:
Proper inflammation resolution is critical for cutaneous wound healing and disordered inflammation resolution results in chronic nonhealing wounds. However, the cellular and molecular mechanisms for resolution of inflammation during skin wound healing are not well understood. MicroRNA-34a is regarded as one tumor suppressor with complexed immune regulatory effects, yet its role during skin wound repair is still unclear.
Methods:
Circular full thickness excisional wounds were made on the dorsal skin of C57 mice and miR-34a expression pattern was examined by real time RT-PCR and in situ hybridization. The wound healing rates and histologic morphometric analysis were quantified and compared between wounds treated with antagomir-34a and autologous control antagomir-NC wounds, as well as wounds between miR-34a knockout (KO) and wild type (WT) mice. Immunohistochemistry (IHC) for both MPO and F4/80 were performed to examine the infiltrative neutrophils and macrophages in wounds from miR-34a KO and WT mice. Cytokines including IL-1β, IL-6, TNF-α and IL-10, were detected and analyzed by real time RT-PCR during wound healing. IHC for IL-6 and p-STAT3 were quantified, and WB for p-STAT3 and IL-6R were examined in wounds of miR-34a KO and WT mice.
Results:
We found miR-34a was significantly downregulated in the inflammatory phase and back to normal levels in the proliferative phase. Both topical knockdown wounds miR-34a levels by antagomir gel and systematic knockout miR-34a using KO mice resulted in impaired wound healing with delayed re-epithelialization and augmented inflammation. IHC results indicated that there were more residual infiltrative inflammatory cells in the proliferative phase. Moreover, over-activated IL-6/STAT3 signal pathway was identified in the wounds of miR-34a KO mice.
Conclusions:
Our findings reveal that miR-34a deficiency augments skin wound inflammation response and leads to impaired wound healing, which suggest that targeted inhibition of miR-34a for tissue repair/regeneration should be with serious consideration.
Insights
MicroRNA-34a (miR-34a) deficiency impairs skin wound healing by increasing inflammation. Targeting miR-34a for tissue repair requires careful consideration due to its role in regulating inflammatory responses.
Area of Science:
- Dermatology
- Immunology
- Molecular Biology
Background:
- Proper inflammation resolution is crucial for effective cutaneous wound healing.
- Disordered inflammation resolution contributes to chronic, nonhealing wounds.
- The role of microRNA-34a (miR-34a) in skin wound repair remains unclear.
Purpose of the Study:
- To investigate the role of miR-34a in the cellular and molecular mechanisms of skin wound healing.
- To determine the impact of miR-34a downregulation on inflammation and healing processes.
Main Methods:
- Excisional wounds were created in C57 mice.
- miR-34a expression was analyzed using RT-PCR and in situ hybridization.
- Wound healing rates, inflammation markers (MPO, F4/80), and cytokine signaling pathways (IL-6/STAT3) were assessed in miR-34a knockdown/knockout models.
Main Results:
- miR-34a was downregulated during the inflammatory phase of wound healing.
- miR-34a deficiency led to impaired re-epithelialization and increased inflammation.
- Overactivation of the IL-6/STAT3 pathway was observed in miR-34a deficient wounds.
Conclusions:
- miR-34a deficiency exacerbates skin wound inflammation and impairs healing.
- Targeted inhibition of miR-34a for tissue repair warrants careful consideration.
