eEF2 improves dense connective tissue repair and healing outcome by regulating cellular death, autophagy, apoptosis, proliferation and migration.
Junyu ChenJin WangXinjie WuNils SimonCamilla I SvenssonJuan YuanDavid A HartAisha S AhmedPaul W AckermannPublished in: Cellular and molecular life sciences : CMLS (2023)
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.Trial registration: NCT02318472 registered 17 December 2014 and NCT01317160 registered 17 March 2011, with URL http://clinicaltrials.gov/ct2/show/NCT02318472 and http://clinicaltrials.gov/ct2/show/study/NCT01317160 .
Keyphrases
- cell death
- patient reported outcomes
- endoplasmic reticulum stress
- cell cycle arrest
- oxidative stress
- endothelial cells
- end stage renal disease
- computed tomography
- single cell
- mass spectrometry
- peritoneal dialysis
- signaling pathway
- transcription factor
- newly diagnosed
- magnetic resonance imaging
- ejection fraction
- induced pluripotent stem cells
- pluripotent stem cells
- chronic kidney disease
- image quality
- stem cells
- risk assessment
- metabolic syndrome
- positron emission tomography
- phase iii
- prognostic factors
- adipose tissue
- clinical trial
- randomized controlled trial
- bone marrow
- label free
- cell proliferation