Resistance exercise and mechanical overload upregulate vimentin for skeletal muscle remodeling

Authors

• Joshua S. Godwin, Auburn University
• J. Max Michel, Auburn University
• Cleiton A. Libardi, Universidade Federal de São Carlos
• Andreas N. Kavazis, Auburn University
• Christopher S. Fry, University of KentuckyFollow
• Andrew D. Frugé, Auburn University
• Mariah McCashland, University of Nebraska–Lincoln
• Ivan J. Vechetti, University of Nebraska–Lincoln
• John J. McCarthy, University of KentuckyFollow
• C. Brooks Mobley, Auburn UniversityFollow
• Michael D. Roberts, Auburn UniversityFollow

Abstract

We adopted a proteomic and follow-through approach to investigate how mechanical overload (MOV) potentially affects novel targets in skeletal muscle, and how a perturbation in this response could potentially affect the adaptive response. First, we determined that 10 wk of resistance training in 15 college-aged females increased sarcolemmal-associated protein content (+10.1%, P < 0.05). Sarcolemmal protein isolates were then queried using mass spectrometry-based proteomics, ∼10% (38/387) of proteins putatively associated with the sarcolemma or extracellular matrix (ECM) were upregulated (>1.5-fold, P < 0.05), and one target (intermediate filament vimentin; VIM) warranted further investigation due to its correlation to myofiber hypertrophy (r = 0.652, P = 0.009). VIM expression was then examined in 4-mo-old C57BL/6J mice following 10 and 20 days of plantaris 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 predominantly resided in the ECM. MOV experiments were replicated in Pax7-DTA (satellite cell depleted) mice, which reduced VIM in the ECM by ∼74%. A third MOV experiment was performed in C57BL/6 mice intramuscularly injected with either AAV9-scrambled (control) or AAV9-VIM-shRNA. Although VIM-shRNA mice possessed lower VIM in the ECM (∼45%), plantaris masses in response to MOV were similar between groups. However, VIMshRNA mice possessed smaller and more centrally nucleated MyHCemb-positive fibers in response to MOV. In summary, skeletal muscle VIM appears to be enriched in the ECM following MOV, satellite cells may regulate its expression, and a disruption in expression during MOV leads to an excessive regenerative phenotype.

Document Type

Article

Publication Date

5-1-2025

Notes/Citation Information

Publisher Copyright: © 2025 The Authors.

Digital Object Identifier (DOI)

10.1152/ajpcell.01028.2024

Archival?

Archival

Repository Citation

Godwin, Joshua S.; Michel, J. Max; Libardi, Cleiton A.; Kavazis, Andreas N.; Fry, Christopher S.; Frugé, Andrew D.; McCashland, Mariah; Vechetti, Ivan J.; McCarthy, John J.; Mobley, C. Brooks; and Roberts, Michael D., "Resistance exercise and mechanical overload upregulate vimentin for skeletal muscle remodeling" (2025). Physiology Faculty Publications. 253.
https://uknowledge.uky.edu/physiology_facpub/253