Integrated transcriptomic and metabolomic analysis reveals arginine-citrulline gene-compound network is critical for severe adhesive capsulitis progression. Integrated transcriptomic and metabolomic analysis reveals arginine-citrulline gene-compound network is critical for severe adhesive capsulitis progression

Adhesive capsulitis (AC) affects 2–5% of the population worldwide. Patients with severe AC fail to regain a complete range of movement and experience years of shoulder pain. Unfortunately, the underlying mechanism of severe AC remains unclear. Here, we performed an integrated transcriptomic and metabolomic data analysis of serum and tissue samples from patients with severe AC, mild AC, and healthy controls. Pathways related to muscle development and myogenesis positively correlated with severe AC progression. Further, we identified an arginine-citrulline gene-compound network that may play a central role in severe AC. Comparing differentially regulated metabolites from tissue and serum, two phospholipids were recognized as potential serum markers for severe AC. In conclusion, this is the first comprehensive integrated -omics study on severe AC and provides insights into genes and compounds of the arginine-citrulline metabolic pathway that may be potential therapeutic targets for treating AC. Overall design: We collected tissues and serum from patients with 13 severe and 12 mild AC and 5 healthy controls. We randomly selected 4 patients from each group and sequenced their proliferative synovium and joint capsule tissues.

粘连性肩关节囊炎（Adhesive capsulitis, AC）全球患病率为2%~5%。重症粘连性肩关节囊炎患者无法恢复全范围肩关节活动，且长期遭受肩部疼痛困扰。遗憾的是，目前重症粘连性肩关节囊炎的潜在发病机制尚未明确。本研究针对重症粘连性肩关节囊炎患者、轻症粘连性肩关节囊炎患者及健康对照者的血清与组织样本，开展了整合转录组学与代谢组学数据分析。研究发现，与肌肉发育及肌发生相关的通路与重症粘连性肩关节囊炎的病情进展呈正相关。此外，本研究还鉴定出一条精氨酸-瓜氨酸基因-化合物网络，其可能在重症粘连性肩关节囊炎中发挥核心调控作用。对比组织与血清中的差异调控代谢物后，本研究确定两种磷脂可作为重症粘连性肩关节囊炎的潜在血清标志物。综上，本研究是首个针对重症粘连性肩关节囊炎的综合性整合组学研究，为精氨酸-瓜氨酸代谢通路中的相关基因与化合物提供了全新见解，这些分子或可成为治疗粘连性肩关节囊炎的潜在治疗靶点。研究设计：本研究共收集13例重症粘连性肩关节囊炎患者、12例轻症粘连性肩关节囊炎患者及5例健康对照者的组织与血清样本。本研究从每组中随机选取4例患者，对其增生性滑膜与关节囊组织进行转录组测序。