Deciphering the Interlinked CXCR4-Mediated Feedback Loop Among Signaling Pathways in Diabetic Wound Healing

Diabetic chronic wounds and amputations are very serious complications of diabetes mellitus (DM) that result from an integration factor, including oxygen deprivation, elevated reactive oxygen species (ROS), reduced angiogenesis, and microbial invasion. These causative factors lead to tenacious wounds in an inflammatory state, which eventually results in tissue aging and necrosis. Wound healing in DM potentially targets C-X-C chemokine receptor type 4 (CXCR4) regulates several signalling pathways. The CXCR4 signalling pathway integrated with phospholipase C (PLC)/protein kinase-C (PKC) Ca²⁺ pathways, stromal cell-derived factor-1 (SDF-1), and mitogen- activated protein kinases (MAPKs) pathway for enhancing cell chemotaxis, proliferation, and survival. The dysregulated CXCR4 pathway is connected with poor wound healing in DM patients. Therapeutic strategies targeting CXCR4-based molecules such as UCUF-728, UCUF-965, and AMD3100 have been shown to enhance diabetic wound healing by altering miRNA expression, promoting angiogenesis, and accelerating wound closure. This study indicates that CXCR4 participation in various signalling pathways makes it essential for understanding the healing of diabetic wounds. Using specific compounds to target CXCR4 offers a potentially effective treatment strategy to improve wound healing in diabetes. Our understanding of CXCR4 signalling and its regulation processes will enable us to develop more potent wound care solutions for diabetic chronic wounds. This report concludes that CXCR4's potential therapeutic targeting shows improvements in diabetic wound repair. This review will demonstrate that CXCR4 plays a major role in wound healing through its various signalling pathways. Targeting CXCR4 with certain agonist molecules shows a therapeutic approach to potentially increasing wound healing in diabetes. By enhancing our understanding of the CXCR4 signalling mechanism in future studies, we can develop more potential treatments for chronic diabetic wounds.