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Updated: Mar 21, 2026
A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes
Amitava Das1, Subhadip Ghatak1, Mithun Sinha1
1Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH 43210; Davis Heart and Lung Research Institute, Ohio State University Wexner Medical Center, Columbus, OH 43210; Comprehensive Wound Center, Center for Regenerative Medicine and Cell Based Therapies, Ohio State University Wexner Medical Center, Columbus, OH 43210;
Abstract:
Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates wound closure. MFG-E8(-/-) mice displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis, and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8(-/-) bone marrow to MFG-E8(+/+) mice resulted in impaired wound closure and compromised wound vascularization. In contrast, MFG-E8(-/-) mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8, recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care.
Insights
Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is crucial for clearing dead cells and healing wounds. Restoring MFG-E8 function in diabetic wounds accelerates closure and reduces inflammation.
Area of Science:
- Biochemistry
- Immunology
- Wound Healing Research
Background:
- Milk fat globule epidermal growth factor-factor 8 (MFG-E8) facilitates efferocytosis, the clearance of apoptotic cells.
- Efferocytosis is impaired in diabetic wound macrophages, hindering healing.
- MFG-E8's role in diabetic wound healing requires further investigation.
Purpose of the Study:
- To investigate the role of MFG-E8 in inflammation resolution, angiogenesis, and wound closure.
- To determine if MFG-E8 deficiency exacerbates diabetic wound healing defects.
- To explore MFG-E8 as a therapeutic target for diabetic wound care.
Main Methods:
- Utilized MFG-E8 knockout (MFG-E8(-/-)) and wild-type mice models.
- Performed bone marrow transplantation experiments to assess MFG-E8's cell-specific contribution.
- Administered topical recombinant MFG-E8 to diabetic mouse models (db/db).
Main Results:
- MFG-E8(-/-) mice exhibited impaired efferocytosis, increased inflammation, and delayed wound closure.
- Wound macrophage-derived MFG-E8 was essential for wound angiogenesis.
- Hyperglycemia and advanced glycated end products inactivated MFG-E8, contributing to diabetic wound complications.
- Topical MFG-E8 treatment resolved inflammation, enhanced angiogenesis, and accelerated wound closure in diabetic mice.
Conclusions:
- MFG-E8 is a critical mediator of efferocytosis, angiogenesis, and wound healing.
- MFG-E8 inactivation by hyperglycemia is a key mechanism underlying diabetic wound impairment.
- MFG-E8 holds significant therapeutic potential for treating diabetic wounds.
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