Dataset Information

Force dependent effects of chronic overuse on fibrosis-related genes and proteins in skeletal muscles.

ABSTRACT:

Aim

To examine the chronic effect of force on mRNA and protein expression levels of fibrosis-related genes in flexor digitorum muscles in a rat model of repetitive overuse injury that induces muscle fibrosis at high force levels.

Materials and methods

Two groups of rats were trained to perform a voluntary repetitive lever-pulling task at either a high (HFHR) or a low force (LFHR) for 18 weeks, while a control group (FRC) performed no task. RNA and protein were prepared from forelimb flexor digitorum muscles. Fibrosis-related gene RNA transcripts were evaluated using quantitative PCR (qPCR) and analyzed using the geometric mean of three housekeeping genes or the mean of each individually as reference. Protein levels were quantified using ELISA, western blot, or immunohistofluorescence.

Results

Of eight fibrosis-related mRNAs examined, only FGF2 demonstrated a consistent significant increase in the HFHR group, compared to the FRC group. However, protein amounts of collagen type 1, collagen type 3, and TGFβ1 were significantly higher in the HFHR, compared to the FRC and LFHR groups, while CCN2 and FGF2 were higher in both HFHR and LFHR, compared to the FRC group.

Conclusions

Our results suggest that there is steady-state transcription of fibrogenic genes in muscles with established fibrosis, implying that post-transcriptional processes are responsible for the increased protein levels of fibrotic factors during muscle overuse conditions. We hypothesize that targeting such pathways represents a valid approach to treat overuse injury. Alternatively, FGF2 gene expression may represent a valid target for therapy.

SUBMITTER: Hilliard BA

PROVIDER: S-EPMC7718395 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveWe reviewed and appraised the existing evidence of in vivo manifestations of residual force enhancement in human skeletal muscles and assessed, through a meta-analysis, the effect of an immediate history of eccentric contraction on the subsequent torque capacity of voluntary and electrically evoked muscle contractions.MethodsOur search was conducted from database inception to May 2020. Descriptive information was extracted from, and quality was assessed for, 45 studies. Meta-analyses and metaregressions were used to analyze residual torque enhancement and its dependence on the angular amplitude of the preceding eccentric contraction.ResultsProcedures varied across studies with regards to muscle group tested, angular stretch amplitude, randomization of contractions, time window analyzed, and verbal command. Torque capacity in isometric (constant muscle tendon unit length and joint angle) contractions preceded by an eccentric contraction was typically greater compared to purely isometric contractions, and this effect was greater for electrically evoked muscle contractions than voluntary contractions. Residual torque enhancement differed across muscle groups for the voluntary contractions, with a significant enhancement in torque observed for the adductor pollicis, ankle dorsiflexors, ankle plantar flexors, and knee extensors, but not for the elbow and knee flexors. Meta-regressions revealed that the angular amplitude of the eccentric contraction (normalized to the respective joint's full range of motion) was not associated with the residual torque enhancement observed.ConclusionThere is evidence of residual torque enhancement for most, but not all, muscle groups, and residual torque enhancement is greater for electrically evoked than for voluntary contractions. Contrary to our hypothesis, and contrary to generally accepted findings on isolated muscle preparations, residual torque enhancement in voluntary and electrically evoked contractions does not seem to depend on the angular amplitude of the preceding eccentric contraction.