eEF2 improves dense connective tissue repair and healing outcome by regulating cellular death, autophagy, apoptosis, proliferation and migration

被引:12
作者
Chen, Junyu [1 ]
Wang, Jin [2 ,3 ]
Wu, Xinjie [1 ,4 ]
Simon, Nils [5 ]
Svensson, Camilla I. [5 ]
Yuan, Juan [6 ]
Hart, David A. [7 ]
Ahmed, Aisha S. [1 ,8 ]
Ackermann, Paul W. [1 ]
机构
[1] Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, S-17176 Stockholm, Sweden
[2] Xi An Jiao Tong Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Pharmacol, Xian 710061, Shaanxi, Peoples R China
[3] Hangzhou Med Coll, Peoples Hosp, Zhejiang Prov Peoples Hosp, Key Lab Tumor Mol Diag & Individualized Med Zhejia, Hangzhou 310014, Peoples R China
[4] Peking Univ China, Japan Friendship Sch Clin Med, Beijing 100029, Peoples R China
[5] Karolinska Inst, Ctr Mol Med, Dept Physiol & Pharmacol, S-17176 Stockholm, Sweden
[6] Karolinska Inst, Dept Cell & Mol Biol, S-17176 Stockholm, Sweden
[7] Univ Calgary, McCaig Inst Bone & Joint Hlth, Fac Kinesiol, Dept Surg, Calgary, AB, Canada
[8] Univ Helsinki, Dept Physiol, Helsinki, Finland
基金
瑞典研究理事会;
关键词
Mass spectrometry; Dense connective tissue repair; Fibroblast; eEF2; Cell biology; Regeneration; PROMOTES; MATRIX; CELLS; INFLAMMATION; INHIBITION; ACTIVATION; DRAFT; AMPK;
D O I
10.1007/s00018-023-04776-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Outcomes following human dense connective tissue (DCT) repair are often variable and suboptimal, resulting in compromised function and development of chronic painful degenerative diseases. Moreover, biomarkers and mechanisms that guide good clinical outcomes after DCT injuries are mostly unknown. Here, we characterize the proteomic landscape of DCT repair following human Achilles tendon rupture and its association with long-term patient-reported outcomes. Moreover, the potential regulatory mechanisms of relevant biomarkers were assessed partly by gene silencing experiments. A mass-spectrometry based proteomic approach quantified a large number (769) of proteins, including 51 differentially expressed proteins among 20 good versus 20 poor outcome patients. A novel biomarker, elongation factor-2 (eEF2) was identified as being strongly prognostic of the 1-year clinical outcome. Further bioinformatic and experimental investigation revealed that eEF2 positively regulated autophagy, cell proliferation and migration, as well as reduced cell death and apoptosis, leading to improved DCT repair and outcomes. Findings of eEF2 as novel prognostic biomarker could pave the way for new targeted treatments to improve healing outcomes after DCT injuries.
引用
收藏
页数:17
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