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Updated: Oct 19, 2025
Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
KLF4 Promotes Diabetic Chronic Wound Healing by Suppressing Th17 Cell Differentiation in an MDSC-Dependent Manner
Xiong Yang1, Bryan J Mathis2, Yu Huang1
1Department of Urology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, China.
Objectives:
Diabetic wound inflammation deficiencies lead to ulcer development and eventual amputation and disability. Our previous research demonstrates that myeloid-derived suppressor cells (MDSCs) accumulate during inflammation and promote chronic wound healing via the regulation of Kruppel-like factor 4 (KLF4). In this study, we aimed to investigate the potential roles of MDSCs and KLF4 in diabetic wound healing.
Methods:
An ob/ob mouse pressure ulcer (PU) model was used to evaluate the process of wound healing. The expression levels of KLF4 and IL-17A were measured by real-time PCR, and the population of MDSCs and Th17 cells was measured by flow cytometry. The levels of cytokines were determined by an immunosuppression assay.
Results:
KLF4 deficiency in the diabetic PU model resulted in decreased accumulation of MDSCs, increased expansion of Th17 cells, and significantly delayed wound healing. Conversely, KLF4 activation by APTO-253 accelerated wound healing accompanied by increased MDSC populations and decreased numbers of Th17 cells. MDSCs have been proven to mediate Th17 differentiation via cytokines, and our in vitro data showed that elevated KLF4 expression in MDSCs resulted in reduced Th17 cell numbers and, thus, decreased levels of cytokines indispensable for Th17 differentiation.
Conclusions:
Our study revealed a previously unreported function of KLF4-regulated MDSCs in diabetic wound healing and identified APTO-253 as a potential agent to improve the healing of pressure ulcers.
Insights
Kruppel-like factor 4 (KLF4) regulates myeloid-derived suppressor cells (MDSCs) to promote diabetic wound healing. Activating KLF4 with APTO-253 accelerates healing in pressure ulcers by modulating MDSCs and Th17 cells.
Area of Science:
- Immunology
- Wound Healing
- Diabetic Complications
Background:
- Diabetic wound inflammation impairs healing, leading to severe complications.
- Myeloid-derived suppressor cells (MDSCs) are implicated in chronic wound inflammation.
- Kruppel-like factor 4 (KLF4) is a key regulator of MDSC function in inflammation.
Purpose of the Study:
- Investigate the roles of MDSCs and KLF4 in diabetic wound healing.
- Determine the therapeutic potential of modulating KLF4 for pressure ulcer treatment.
Main Methods:
- Utilized an ob/ob mouse pressure ulcer (PU) model.
- Quantified KLF4, IL-17A, MDSCs, and Th17 cells using real-time PCR and flow cytometry.
- Assessed cytokine levels via immunosuppression assays.
Main Results:
- KLF4 deficiency delayed wound healing, decreased MDSCs, and increased Th17 cells.
- APTO-253 treatment accelerated healing, increased MDSCs, and reduced Th17 cells.
- In vitro studies confirmed KLF4's role in suppressing Th17 differentiation via cytokines.
Conclusions:
- KLF4-regulated MDSCs play a critical role in diabetic wound healing.
- APTO-253 demonstrates potential as a therapeutic agent for pressure ulcer healing.
