Skeletal muscle regeneration is hindered in severe injuries and degenerative diseases, including
volumetric muscle loss (VML), due to the failure of current treatments to induce functional tissue
growth. Various biological functions in skeletal muscle are supported by the extracellular matrix
(ECM), a collection of proteins and glycosaminoglycans. <i>In vivo</i> studies on murine plantaris
muscle hypertrophy indicate that ECM remodeling facilitates muscle growth, but a global analysis
of ECM protein dynamics during skeletal muscle hypertrophy and repair are unknown.
Understanding this influence of the ECM can establish instructive cues for regenerative therapies.
Here, we define global proteomic changes throughout stages of plantaris muscle hypertrophy, with
an emphasis on characterizing ECM proteins. Synergistic ablation of the gastrocnemius and soleus
muscles induced a compensatory hypertrophic effect causing a 40% mass increase in the plantaris
muscle 28 days post injury. Liquid chromatography-tandem mass spectrometry revealed the
differential abundance of 1233 proteins, including 99 ECM proteins, across five time points. After
two days of injury, a significant increase of ECM glycoproteins was observed although the overall
collagen abundance decreased. Throughout the duration of injury, the relative abundance of type
I collagen decreased while there was an increase of proteins associated with type I collagen
fibrillogenesis (types III and V) and basement membrane (types IV and VI). Collectively, these
results provide a better understanding of ECM dynamics throughout skeletal muscle hypertrophy.
Future studies will evaluate protein synthesis by using non-canonical amino acids to identify newly
synthesized proteins. Temporal analysis of protein dynamics symbolic to injury and tissue growth
will provide tissue engineers with precise information to develop successful regenerative therapies
to restore functional muscle in VML.
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/12253061 |
| Date | 07 May 2020 |
| Creators | Alita Frances Miller (8803271) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Identifying_Extracellular_Matrix_Protein_Dynamics_in_Skeletal_Muscle_Hypertrophy_for_Regenerative_Therapies/12253061 |
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