Qianman Bayixiati, Jiasharete Tuomilisi, Badalihan Ayinazi, Mamately Abuduhilil, Yeerbo Naertai, Bahesutihan Yemenlehan, Wupuer Aikeremu, Aisaiding Amuding, Wuerliebieke Jianati, Jialihasi Ayidaer, Li Ping, Jielile Jiasharete
Department of Osteopathy and Orthopedics (Ankle) Surgery, The Sixth Teaching Hospital of Xinjiang Medical University, No. 39 Wuxing South Road, Urumqi 830001, Xinjiang Uygur Autonomous Region, China.
Department of Clinical Medicine, Capital Medical University Class of 2024, Five-Year Clinical Medicine Class 3, No. 10, Xitoutiao, You'anmenwai, Fengtai District, Beijing 100069, China.
J Proteome Res. 2025 Jan 3;24(1):65-76. doi: 10.1021/acs.jproteome.4c00357. Epub 2024 Nov 27.
Spontaneous Achilles tendon rupture (SATR) predominantly affects middle-aged and elderly individuals with chronic injuries. However, the exact cause and mechanism of SATR remain elusive, and potential therapeutic intervention or prevention is still insufficient. The present study aimed to uncover the key pathological molecules by using iTRAQ proteomics. The results identified 2432 candidate proteins in SATR patients using iTRAQ proteomic analysis. A total of 307 differentially expressed proteins (DEPs) were identified and linked to 211 KEGG signaling pathways including Coronavirus disease (COVID-19), focal adhesion, and ribosomes. GO enrichment analysis highlighted significant enrichment in processes such as biological adhesion, ossification, lipid (APOA4) processes, and extracellular matrix (ECM) organization (collagen). PPI network analysis identified hub genes such as serum albumin (ALB), fibronectin (FN1), and actin cytoplasmic 1. The WB analysis confirmed that FN1 and the receptor for activated C kinase (RACK1) were downregulated in the SATR tendon. Immunohistochemical staining revealed that collagen I and III were suppressed, while collagen II and APOA4 expression were higher in the SATR pathological tissue ( < 0.05). However, the primary cultured tenocytes (PCTs) from SATR patients showed enhanced proliferation and, consistent with tissue staining, reduced collagen I and III and increased collagen II. Our findings reveal vital targets and pathways in SATR's etiological progression, offering a new perspective on the diagnosis, treatment, and prognosis of this complex disorder.
自发性跟腱断裂（SATR）主要影响患有慢性损伤的中老年人。然而，SATR的确切病因和机制仍不清楚，潜在的治疗干预或预防措施也仍然不足。本研究旨在通过iTRAQ蛋白质组学揭示关键的病理分子。结果通过iTRAQ蛋白质组学分析在SATR患者中鉴定出2432种候选蛋白。共鉴定出307种差异表达蛋白（DEP），并与包括冠状病毒病（COVID-19）、粘着斑和核糖体在内的211条KEGG信号通路相关联。基因本体（GO）富集分析突出显示在生物粘附、骨化、脂质（载脂蛋白A4）过程和细胞外基质（ECM）组织（胶原蛋白）等过程中有显著富集。蛋白质-蛋白质相互作用（PPI）网络分析确定了血清白蛋白（ALB）、纤连蛋白（FN1）和肌动蛋白细胞质1等枢纽基因。蛋白质免疫印迹（WB）分析证实，FN1和活化C激酶受体（RACK1）在SATR肌腱中表达下调。免疫组织化学染色显示，SATR病理组织中I型和III型胶原蛋白受到抑制，而II型胶原蛋白和载脂蛋白A4表达较高（P<0.05）。然而，来自SATR患者的原代培养肌腱细胞（PCT）增殖增强，并且与组织染色结果一致，I型和III型胶原蛋白减少，II型胶原蛋白增加。我们的研究结果揭示了SATR病因进展中的关键靶点和途径，为这种复杂疾病的诊断、治疗和预后提供了新的视角。
