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Updated: Nov 18, 2025
Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
MicroRNA-146a Deficiency Delays Wound Healing in Normal and Diabetic Mice
Xinling Bi1,2, Li Zhou2, Yanfang Liu3
1Department of Dermatology, Changhai Hospital, Naval Medical University, Shanghai, China.
Abstract:
Objective: MiRNAs are important regulators of inflammation and wound healing. However, the mechanisms through which miRNAs regulate wound healing under normal and diabetic conditions are poorly understood. We aimed to determine the effects of miR-146a on the pathogenesis of wound healing in normal and streptozotocin (STZ)-induced diabetic mice. Approach: Wild-type (WT) and miR-146a knockout (KO) mice were induced to develop diabetes with STZ. Next, skin and corneal wounds were produced and measured. Percent wound closure and histology were evaluated. Inflammation at wound sites was analyzed using flow cytometry, reverse-transcription PCR, and western blot. Results: Healing of wounded skin was significantly delayed in miR-146a KO compared with WT mice. However, corneal epithelial wound healing did not differ significantly in the mice with normal blood glucose, whereas corneal and skin wound healing was significantly delayed in KO mice with diabetes. Neutrophil infiltration increased in skin wounds of KO compared with normal mice. The potential mechanisms were associated with dysregulated interleukin 1β, tumor necrosis factor alpha (TNF-α), IRAK1 (interleukin-1 receptor-associated kinase 1), TRAF6 (TNF receptor-associated factor 6), and nuclear factor kappa B (NF-κB) signaling induced by miR-146a KO. Innovation: Skin wound healing was delayed in miR-146a KO mice and enhanced inflammatory responses were mediated by the NF-κB signaling pathway. Conclusions: Deficiency in miR-146a delayed skin wound healing by enhancing inflammatory responses in normal and diabetic mice. Therefore, miR-146a may be a potential target for modulation to accelerate skin wound healing.
Insights
MicroRNA-146a (miR-146a) deficiency delays skin wound healing by increasing inflammation. Restoring miR-146a function could accelerate healing in both normal and diabetic conditions.
Area of Science:
- Molecular Biology
- Immunology
- Regenerative Medicine
Background:
- MicroRNAs (miRNAs) are crucial regulators of biological processes, including inflammation and wound healing.
- The specific roles of miRNAs, like miR-146a, in wound healing, especially under diabetic conditions, remain incompletely understood.
Purpose of the Study:
- To investigate the impact of miR-146a deficiency on skin and corneal wound healing in normal and diabetic mouse models.
- To elucidate the underlying molecular mechanisms, particularly the involvement of inflammatory signaling pathways.
Main Methods:
- Utilized wild-type and miR-146a knockout mice, inducing diabetes with streptozotocin (STZ).
- Assessed skin and corneal wound closure, histology, and inflammatory markers (flow cytometry, RT-PCR, Western blot).
- Analyzed key inflammatory mediators and signaling pathways, including NF-κB.
Main Results:
- miR-146a knockout significantly delayed skin wound healing in both normal and diabetic mice.
- Corneal wound healing was impaired in diabetic miR-146a knockout mice.
- Increased neutrophil infiltration and dysregulated inflammatory signaling (IL-1β, TNF-α, IRAK1, TRAF6, NF-κB) were observed in knockout mice.
Conclusions:
- miR-146a deficiency exacerbates inflammatory responses, leading to delayed skin wound healing.
- miR-146a plays a protective role in wound healing by modulating inflammation.
- Targeting miR-146a presents a potential therapeutic strategy for accelerating skin wound healing.
