Dataset Information

Targeted exercise enhances functional integration of engineered muscle grafts after volumetric muscle loss

ABSTRACT: Damage that affects large volumes of skeletal muscle tissue can severely impact health, mobility, and quality-of-life. Efforts to restore muscle function by implanting engineered grafts at the site of damage have demonstrated limited restoration of force production. Various forms of mechanical and biochemical stimulation have been shown to have a potentially beneficial impact on muscle maturation, vascularization, and innervation, but yield unpredictable and inconsistent recovery of functional mobility. Here we show that targeted exercise of optogenetic engineered muscle grafts restores motor functions 2 weeks post-injury. Furthermore, we conduct phosphoproteomic analysis of grafts in vitro and in vivo to show that exercise training alters signaling pathways that play key roles in skeletal muscle contractility, neurite growth, neuromuscular synapse formation, angiogenesis, and cytoskeletal remodeling. Our study uncovers several proteins not previously known to be modulated by exercise, revealing promising mechanisms for leveraging targeted exercise to enhance functional integration of tissue engineered muscle.

INSTRUMENT(S): Q Exactive Plus, Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Muscle, Skeletal Muscle Myoblast In Skeletal Muscle

SUBMITTER: Tigist Tamir

LAB HEAD: Forest M White

PROVIDER: PXD039237 | Pride | 2025-05-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	TYT_20211107_implant_invivo_TMTpro_pY-_1_.mzML	Mzml
	TYT_20211107_implant_invivo_TMTpro_pY-_1_.mzid.gz	Mzid
	TYT_20211107_implant_invivo_TMTpro_pY.raw	Raw
	TYT_20211107_implant_invivo_TMTpro_sup-_1_.mzML	Mzml
	TYT_20211107_implant_invivo_TMTpro_sup-_1_.mzid.gz	Mzid

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Publications

Actuated tissue engineered muscle grafts restore functional mobility after volumetric muscle loss.

Rousseau Erin E Raman Ritu R Tamir Tigist T Bu Angel A Srinivasan Shriya S Lynch Naomi N Langer Robert R White Forest M FM Cima Michael J MJ

Biomaterials 20230908

Damage that affects large volumes of skeletal muscle tissue can severely impact health, mobility, and quality-of-life. Efforts to restore muscle function by implanting tissue engineered muscle grafts at the site of damage have demonstrated limited restoration of force production. Various forms of mechanical and biochemical stimulation have been shown to have a potentially beneficial impact on graft maturation, vascularization, and innervation. However, these approaches yield unpredictable and in ...[more]

PMID: 37717406

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Project description:Purpose. Insulin resistant muscle is resistant to gene expression changes induced by acute exercise. This study was undertaken to identify transcription factors that differentially respond to exercise in insulin resistance. Candidate transcription factors were identified from analysis of 5’-untranslated regions (5’-UTRs) of exercise responsive genes and from analysis of the 5’-UTRs of genes coding for proteins that differ in abundance in insulin resistance. Research design and methods. Muscle biopsies were obtained from lean and obese subjects before and after a single exercise bout. Euglycemic glucose clamps assessed insulin sensitivity. Global proteomics analysis identified differentially abundant proteins. The 5’-UTRs of genes coding for significant proteins were subjected to transcription factor enrichment analysis to identify candidate transcription factors. Q-rt-PCR to determine expression of candidate transcription factors was performed on RNA from resting and post-exercise muscle biopsies; immunoblots quantified protein abundance. Results. Obese subjects were insulin resistant compared to lean but performed exercise at the same intensity. Proteins involved in mitochondrial function, protein targeting and translation, and metabolism were among those significantly different between the groups. Transcription factor enrichment analysis of genes coding for these proteins revealed new candidate transcription factors. Q-rt-PCR analysis of RNA and immunoblot analysis from pre- and post-exercise muscle biopsies revealed several transcription and growth factors that had altered responses to exercise in insulin resistant subjects. Conclusions. These results confirm findings of an association between insulin sensitivity and transcription factor mRNA response to exercise and extend these results to show that obesity also may be a sufficient prerequisite for exercise resistance. Analysis of the muscle proteome together with determination of effects of exercise on expression of transcription factors suggests that abnormal responses of transcription factors to exercise may be responsible for differences in protein abundances in insulin resistant muscle.