Resistance Exercise and Mechanical Overload Upregulate Vimentin for Skeletal Muscle Remodeling

Godwin, J. S.; Michel, J. M.; Libardi, C. A.; Kavazis, A. N.; Fry, C. S.; Fruge, A. D.; McCashland, M.; Vechetti, I. J.; McCarthy, J. J.; Mobley, C. B.; Roberts, M. D.

doi:10.1101/2024.06.03.597241

bioRxiv · 10.1101/2024.06.03.597241

Resistance Exercise and Mechanical Overload Upregulate Vimentin for Skeletal Muscle Remodeling

Godwin, J. S.·Michel, J. M.·Libardi, C. A.·Kavazis, A. N.·Fry, C. S.·Fruge, A. D.·McCashland, M.·Vechetti, I. J.·McCarthy, J. J.·Mobley, C. B.·Roberts, M. D.

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Abstract

Our laboratory has performed various experiments examining the proteomic alterations that occur with mechanical overload (MOV)-induced skeletal muscle hypertrophy. In the current study we first sought to determine how 10 weeks of resistance training in 15 college-aged females affected protein concentrations in different tissue fractions. Training, which promoted significantly lower body muscle- and fiber-level hypertrophy, notably increased sarcolemmal/membrane protein content (+10.1%, p<0.05). Sarcolemmal/membrane protein isolates were queried using mass spectrometry-based proteomics, [~]10% (38/387) of proteins associated with the sarcolemma were up-regulated (>1.5-fold, p<0.05), and one of these targets (the intermediate filament vimentin; VIM) warranted further mechanistic investigation. VIM expression was first examined in the plantaris muscles of 4-month-old C57BL/6J mice following 10- and 20-days of MOV via synergist ablation. Relative to Sham (control) mice, VIM mRNA and protein content was significantly higher in MOV mice and immunohistochemistry indicated that VIM was predominantly present in the extracellular matrix (ECM). The 10- and 20-day MOV experiments were replicated in Pax7-DTA (tamoxifen-induced, satellite cell depleted) mice, which reduced the presence of VIM in the ECM. Finally, a third set of 10- and 20-day MOV experiments were performed in C57BL/6 mice intramuscularly injected with either AAV9-scrambled (control) or AAV9-VIM shRNA. While VIM shRNA mice presented with lower VIM in the ECM ([~]50%), plantaris masses in response to MOV were similar between the injection groups. However, VIM shRNA mice presented with appreciably more MyHCemb-positive fibers with centrally located nuclei, indicating a regenerative phenotype. Using an integrative approach, we propose that skeletal muscle VIM is a mechanosensitive target predominantly localized to the ECM, and satellite cells are involved in its expression. Moreover, a disruption in VIM expression during MOV leads to dysfunctional skeletal muscle hypertrophy.

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Godwin, J. S., Michel, J. M., Libardi, C. A., Kavazis, A. N., Fry, C. S., Fruge, A. D., McCashland, M., Vechetti, I. J., McCarthy, J. J., Mobley, C. B., Roberts, M. D.. 2024-06-03. Resistance Exercise and Mechanical Overload Upregulate Vimentin for Skeletal Muscle Remodeling. https://doi.org/10.1101/2024.06.03.597241

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