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

Authors
  • Chen, Junyu
  • Wang, Jin
  • Wu, Xinjie
  • Simon, Nils
  • Svensson, Camilla I.
  • Yuan, Juan
  • Hart, David A.
  • Ahmed, Aisha S.
  • Ackermann, Paul W.
Type
Published Article
Journal
Cellular and Molecular Life Sciences
Publisher
Springer-Verlag
Publication Date
Apr 21, 2023
Volume
80
Issue
5
Identifiers
DOI: 10.1007/s00018-023-04776-x
PMID: 37084140
PMCID: PMC10121543
Source
PubMed Central
Keywords
Disciplines
  • Original Article
License
Unknown

Abstract

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 . Supplementary Information The online version contains supplementary material available at 10.1007/s00018-023-04776-x.

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