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Updated: Jul 15, 2026
Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.
Published on: March 25, 2020
Macrophage Dicer1 deletion delays skin wound healing in mice by promoting pentose phosphate pathway activity
Jiwen Zheng1, Di Tian2, Hong Chen1
1Department of Orthopedics, NO. 903 Hospital of People's Liberation Army (PLA) Joint Logistic Support Force, Hangzhou, Zhejiang Province, China.
Background:
Macrophages play a pivotal role in skin wound healing through efferocytosis, the clearance of apoptotic cells, which is essential for inflammation resolution and tissue repair. This study aims to investigate the role of macrophage Dicer1 in skin wound healing in mice and to explore the regulatory mechanism underlying efferocytosis.
Methods:
Dorsal skin wounds were created in Dicer1-deficient and wild type mice, and the wound areas were quantified daily. In the wounds, epithelialization, granulation tissue growth, collagen deposition, angiogenesis, and the mRNA levels of inflammatory cytokines were measured and apoptotic cells were labelled. In vitro, macrophages were separated from the wounds, and the expressions of pentose phosphate pathway (PPP)-related molecules were measured; wound macrophages were cocultured with apoptotic Jurkat cells, then the phagocytosis was analyzed, and the mRNA levels of inflammatory cytokines and PPP-related molecules were measured in the macrophages.
Results:
Macrophage-specific deletion of Dicer1 impairs skin wound healing in mice, resulting in delayed wound closure, reduced re-epithelialization and granulation tissue formation, diminished collagen deposition, and attenuated angiogenesis. Dicer1-deficient wounds exhibited sustained inflammation, alongside increased apoptotic cell accumulation. Mechanistically, Dicer1 knockout in macrophages led to impaired efferocytosis and upregulated PPP activity.
Conclusion:
These findings identify the Dicer1-PPP-efferocytosis axis as a critical regulator of macrophage function during wound repair. Our study provides novel insights into the molecular basis of impaired wound healing and suggests that targeting the macrophage Dicer1-PPP-efferocytosis axis may offer therapeutic potential for skin wounds.
Insights
Macrophage Dicer1 is crucial for skin wound healing. Its deficiency impairs efferocytosis and delays repair by upregulating the pentose phosphate pathway (PPP). Targeting this axis may improve wound healing therapies.
Area of Science:
- Immunology
- Molecular Biology
- Dermatology
Background:
- Macrophages are vital for skin wound healing, performing efferocytosis to resolve inflammation and promote tissue repair.
- Dicer1, an enzyme involved in microRNA processing, is investigated for its role in macrophage function during wound healing.
- Efferocytosis, the clearance of apoptotic cells by macrophages, is a key process in effective tissue regeneration.
Purpose of the Study:
- To investigate the role of macrophage Dicer1 in murine skin wound healing.
- To elucidate the regulatory mechanisms of efferocytosis involving Dicer1.
- To explore the connection between Dicer1, the pentose phosphate pathway (PPP), and macrophage-mediated efferocytosis.
Main Methods:
- Dorsal skin wounds were induced in Dicer1-deficient and wild-type mice for comparative analysis.
- Wound healing parameters including closure, epithelialization, collagen deposition, and angiogenesis were quantified.
- Macrophages were isolated from wounds for in vitro analysis of efferocytosis, PPP activity, and inflammatory cytokine expression.
Main Results:
- Macrophage-specific Dicer1 deficiency significantly impaired skin wound healing, characterized by delayed closure and reduced tissue regeneration.
- Dicer1 knockout in macrophages resulted in impaired efferocytosis and increased accumulation of apoptotic cells.
- Upregulated pentose phosphate pathway (PPP) activity was observed in Dicer1-deficient macrophages, correlating with impaired efferocytosis.
Conclusions:
- The Dicer1-PPP-efferocytosis axis is identified as a critical regulator of macrophage function in skin wound repair.
- Dysregulation of this axis contributes to impaired wound healing.
- Targeting the macrophage Dicer1-PPP-efferocytosis pathway presents a potential therapeutic strategy for enhancing skin wound healing.
