Journal of Inflammation Research (Mar 2024)
The Mechanism of Pyroptosis and Its Application Prospect in Diabetic Wound Healing
Abstract
Abdullah Al Mamun,1,2 Chuxiao Shao,1 Peiwu Geng,1 Shuanghu Wang,1 Jian Xiao2,3 1Central Laboratory of the Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui City, Zhejiang, 323000, People’s Republic of China; 2Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Wound Healing, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Jian Xiao, Email [email protected]: Pyroptosis defines a form of pro-inflammatory-dependent programmed cell death triggered by gasdermin proteins, which creates cytoplasmic pores and promotes the activation and accumulation of immune cells by releasing several pro-inflammatory mediators and immunogenic substances upon cell rupture. Pyroptosis comprises canonical (mediated by Caspase-1) and non-canonical (mediated by Caspase-4/5/11) molecular signaling pathways. Numerous studies have explored the contributory roles of inflammasome and pyroptosis in the progression of multiple pathological conditions such as tumors, nerve injury, inflammatory diseases and metabolic disorders. Accumulating evidence indicates that the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome results in the activation of pyroptosis and inflammation. Current evidence suggests that pyroptosis-dependent cell death plays a progressive role in the development of diabetic complications including diabetic wound healing (DWH) and diabetic foot ulcers (DFUs). This review presents a brief overview of the molecular mechanisms underlying pyroptosis and addresses the current research on pyroptosis-dependent signaling pathways in the context of DWH. In this review, we also present some prospective therapeutic compounds/agents that can target pyroptotic signaling pathways, which may serve as new strategies for the effective treatment and management of diabetic wounds.Keywords: diabetes mellitus, diabetic wound healing, pyroptosis, NLRP3, caspase-1, GSDMD, inflammation, inflammasome
