Chen Liangwen, Tang Ziqiao, Fu Liangliang, Xie Yang, Xu Junyi, Xia Haibin, Xia Ting, Wang Min
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
Center for Prosthodontics and Implant Dentistry, Optics Valley Branch, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
J Inflamm Res. 2024 Mar 12;17:1621-1642. doi: 10.2147/JIR.S450706. eCollection 2024.
Peri-implantitis (PI) is a prevalent complication of implant treatment. Pyroptosis, a distinctive inflammatory programmed cell death, is crucial to the pathophysiology of PI. Despite its importance, the pyroptosis-related genes (PRGs) influencing PI's progression remain largely unexplored.
This study conducted histological staining and transcriptome analyze from three datasets. The intersection of differentially expressed genes (DEGs) and PRGs was identified as pyroptosis-related differentially expressed genes (PRDEGs). Functional enrichment analyses were conducted to shed light on potential underlying mechanisms. Weighted Gene Co-expression Network Analysis (WGCNA) and a pyroptotic macrophage model were utilized to identify and validate hub PRDEGs. Immune cell infiltration in PI and its relationship with hub PRDEGs were also examined. Furthermore, consensus clustering was performed to identify new PI subtypes. Protein-protein interaction (PPI) network, competing endogenous RNA (ceRNA) network, mRNA-mRNA binding protein regulatory (RBP) network, and mRNA-drugs regulatory network of hub PRDEGs were also analyzed.
Eight hub PRDEGs were identified: , and , which are instrumental in the PI's progression. Two PI subtypes were distinguished, with Cluster 1 exhibiting higher immune cell activation. The exploration of regulatory networks provided novel mechanisms and therapeutic targets in PI.
Our research highlights the critical role of pyroptosis and identifies eight hub PRDEGs in PI's progression, offering insights into novel immunotherapy targets and laying the foundation for advanced diagnostic and treatment strategies. This contributes to our understanding of PI and underscores the potential for personalized clinical management.
种植体周围炎（PI）是种植治疗中一种常见的并发症。焦亡是一种独特的炎症程序性细胞死亡，对PI的病理生理学至关重要。尽管其很重要，但影响PI进展的焦亡相关基因（PRGs）在很大程度上仍未被探索。
本研究对三个数据集进行了组织学染色和转录组分析。将差异表达基因（DEGs）与PRGs的交集确定为焦亡相关差异表达基因（PRDEGs）。进行功能富集分析以阐明潜在的潜在机制。利用加权基因共表达网络分析（WGCNA）和焦亡巨噬细胞模型来识别和验证关键PRDEGs。还研究了PI中的免疫细胞浸润及其与关键PRDEGs的关系。此外，进行了一致性聚类以识别新的PI亚型。还分析了关键PRDEGs的蛋白质-蛋白质相互作用（PPI）网络、竞争性内源RNA（ceRNA）网络、mRNA- mRNA结合蛋白调控（RBP）网络和mRNA-药物调控网络。
确定了八个关键PRDEGs： ， ， ， ， ， ， 和 ，它们在PI的进展中起重要作用。区分出两种PI亚型，其中簇1表现出更高的免疫细胞激活。对调控网络的探索为PI提供了新的机制和治疗靶点。
我们的研究突出了焦亡的关键作用，并在PI的进展中识别出八个关键PRDEGs，为新型免疫治疗靶点提供了见解，并为先进的诊断和治疗策略奠定了基础。这有助于我们对PI的理解，并强调了个性化临床管理的潜力。
