Lactobacillus Plantarum Promotes Wound Healing by Inhibiting the NLRP3 Inflammasome and Pyroptosis Activation in Diabetic Foot Wounds

Abstract

Xiaojun Wang, Xu Li, Jianjun Liu, Yue Tao, Tao Wang, Limeng Li Vascular Surgery, Fudan University Zhongshan Hospital Qingpu Branch, Shanghai, People’s Republic of ChinaCorrespondence: Xu Li, Department of Vascular Surgery, Fudan University Zhongshan Hospital Qingpu Branch, 1158 East Park Road, Qingpu District, Shanghai, 201700, People’s Republic of China, Email [email protected]: Diabetic foot ulcer (DFU) impairs the quality of life of diabetic patients and overburdens healthcare systems and society. It is crucial to comprehend the pathophysiology of DFU and develop effective treatment strategies. The aim of this study was to to evaluate the therapeutic potential of Lactobacillus Plantarum (LP) on wound healing in DFU and to explore the underlying mechanisms.Methods: To investigate the effects of LP on wound healing, human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs) and used to assess cell viability, migration, and pyroptosis using CCK-8, cell scratch, and flow cytometry. The levels of IL-1β and IL-18 were measured by ELISA. The expression of NLRP3, caspase-1 p20, and GSDMD-N was detected by Western blot. Additionally, NLRP3 inhibitor MCC950 was used to treat a diabetic rat model established by streptozotocin (STZ). Pearson correlation analysis was performed to analyze the relationship between LP and NLRP3, IL-1β, IL-18 in ulcer tissue.Results: Our data mechanistically demonstrate that AGEs activate the NLRP3/Caspase-1/GSDMD pathway, leading to an increase in the levels of IL-1β and IL-18 and ultimately promoting cell pyroptosis. Furthermore, we identified that LP inhibits the effects of AGEs by downregulating NLRP3 inflammasome activity. LP facilitated wound healing in diabetic rats and resulted in decreased protein levels of NLRP3 and its downstream target caspase-1 p20. Finally, we observed a negative correlation between LP and NLRP3, IL-1β, IL-18 in diabetic foot skin tissue.Conclusion: Our findings uncovered a novel role of LP in diabetic foot wound healing via regulation of the NLRP3 inflammasome, suggesting this link as a therapeutic target. In future research, it would be valuable to explore the signaling cascades involved in LP-mediated inhibition of NLRP3 inflammasome activation.Keywords: lactobacillus plantarum, AGEs, NLRP3 inflammasome, diabetic foot wounds, pyroptosis

Keywords

• lactobacillus plantarum
• ages
• nlrp3 inflammasome
• diabetic foot wounds
• pyroptosis