Therapeutic strategies targeting the AGE-RAGE axis to promote wound healing in diabetes.
| Study | Model | Strategy | Mechanisms/Outcomes |
|---|---|---|---|
| Anti-RAGE antibody [84] | Diabetic male C57BL/6 mice | Topical application of the RAGE antibody on the wound | ↑ Neutrophil phagocytosis by macrophages.↑ Phenotypic switch to M2 macrophages.Enhanced wound healing. |
| RAGE406R [85]* | Diabetic mice | Prevents the formation of the RAGE-DIAPH1 complex | Accelerate wound healing.Decrease systemic inflammation. |
| Cinnamaldehyde [86] | C57BL/J6 diabetic mice | Daily intraperitoneal injections of cinnamaldehyde | Improved wound healing.Accelerated wound closure.↓ Inflammatory infiltration and oxidative stress.↑ CD31 expression (angiogenesis).M1 to M2 polarization. |
| Resina Draconis hydrogel [87] | RAW264.7 cellMale C57BL/6J diabetic mice | Hydrogels were applied to the wounds | Accelerated wound healing.↓ Oxidative stress.↑ M2 macrophage polarization. |
| RAGE229 [88] | Murine and human SMCsBTBR ob/ob mice | Topical injection of RAGE229 two times daily | ↓ Expression of TNF-α, IL-6, and CCL2/JE-MCP-1.Accelerate wound healing. |
| Palladium hydride (PATP) hydrogel [89] | Male C57BL/6 diabetic mice | Co-blocks the HMGB1-RAGE axis “head-to-tail” (upstream and downstream both)PATP hydrogels were applied to the wounds | ↓ TNF-α, iNOS, and IL-1α levels in the wound.↓ ROS, RAGE, and HMGB1 levels.Promotes wound healing with normal skin architecture.Increased neovascularization. |
| Dang-Gui-Si-Ni [90] | Male Sprague-Dawley diabetic rats | Oral gavage to rats after wounding | Accelerated wound healing.Decreased inflammation (↓ IL-1β, IL-6, TNF-α, AGEs, and RAGE levels).Modulated (↑) TGF-β1 and Smad2/3 protein expression. |
| Dracorhodin [91] | Sprague-Dawley diabetic rats | Wounds were treated with dracorhodin | Accelerated wound healing in a dose-dependent manner.↑ Collagen synthesis, angiogenesis, and growth factor levels.↓ Inflammation and ROS levels. |
| Antimicrobial hydrogel with RAGE and MMP-9 inhibitors [92] | In vitro cell (RAW 264.7) and in vivo diabetic Wistar rat wound model | Immuno-gel was applied to wounds | Significantly decreased MMP-9 and NF-κB expression.Enhanced M2 macrophages and pro-healing cytokines. |
| Rosiglitazone and S-nitroso glutathione (nanoparticles/hydrogel composite) [93] | Diabetic SD rats | RAGE inhibitor/exogenous nitric oxide dressing to the wound every other day | Significantly improved wound healing.↑ Wound closure rate, collagen fiber production, and angiogenesis.↓ Inflammation (↓ IL-1β, TNF-α, and IL-6). |
| GPP@ZnBG hydrogels [94] | Diabetic mice and human subjects | Hydrogel was applied to the wound in mice and to DFUs in humans | ↑ Angiogenesis, collagen formation, and tissue repair.↓ Inflammation.Promote wound repair.Have antibacterial effects. |
* Article preview only is available. DIAPH1: diaphanous-related formin 1; TNF-α: tumor necrosis factor alpha; IL: interleukin; NF-κB: nuclear factor kappa beta; ROS: reactive oxygen species; HMGB1: high-mobility group box protein 1; AGEs: advanced glycation end products; RAGE: receptor for advanced glycation end products; iNOS: inducible nitric oxide synthase; CCL2: C-C motif chemokine ligand 2; MCP-1: monocyte chemoattractant protein-1; TGF-β: transforming growth factor beta.
VR: Conceptualization, Visualization, Writing—original draft, Writing—review & editing. The author read and approved the submitted version.
The author declares that there are no conflicts of interest.
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The authors received no specific funding for this study.
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