Role of Intramuscular PAI-1 During Aged Skeletal Muscle Regeneration

Standing

Undergraduate

Type of Proposal

Oral Presentation

Faculty

Faculty of Human Kinetics

Faculty Sponsor

Dr. Matthew Krause

Proposal

Role of Intramuscular PAI-1 During Aged Skeletal Muscle Regeneration S.A. Angus, F.A. Rahman & M.P. Krause Department of Kinesiology, University of Windsor, ON N9B 3P4, Canada. Primary author: anguss@uwindsor.ca Introduction: Skeletal muscle regeneration is a crucial process in returning muscle to its original function following damage. The accumulation of the extracellular matrix (ECM) is an important, yet often overlooked aspect during the regeneration process. With age, there is a decline in the regenerative capacity of skeletal muscle, partly attributed to the accumulation of the ECM, called fibrosis. Therefore, investigation into the contributors of fibrosis, namely plasminogen activator inhibitor-1 (PAI-1), is needed to better understand changes in the ECM during regeneration in aged muscle.

Methods: Young (3 month old) and aged (18 month old) male C57BL/6J mice were studied (n = 15). Muscle damage was induced via cardiotoxin (CTX) injection to the left tibialis anterior muscle. Mice were sacrificed at 3, 5 and 7 days following damage and muscles were collected. Immunohistochemical (IHC) techniques were used to investigate regenerative capacity, macrophage density, and macrophage-derived PAI-1 expression. A two-way ANOVA was used to determine statistical significance for the results.

Results: Myogenic potential of aged skeletal muscle was found to be significantly lower in the 7-day post-damage compared to young (main effect: p < 0.05). In addition, a significant increase in macrophage count at 7-day post-damage in aged skeletal muscle was observed. There was a significant difference in macrophage-derived PAI-1 content throughout the regeneration process between groups (p < 0.05). Discussion: Aged skeletal muscle was observed to have a diminished regenerative capacity as well as an increase in prolonged necrosis following damage. These findings suggest that the implications of macrophage-derived PAI-1 may have a negative effect on the ECM and the regenerative capacity of aged skeletal muscle.

Location

University of Windsor

Grand Challenges

Viable, Healthy and Safe Communities

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Role of Intramuscular PAI-1 During Aged Skeletal Muscle Regeneration

University of Windsor

Role of Intramuscular PAI-1 During Aged Skeletal Muscle Regeneration S.A. Angus, F.A. Rahman & M.P. Krause Department of Kinesiology, University of Windsor, ON N9B 3P4, Canada. Primary author: anguss@uwindsor.ca Introduction: Skeletal muscle regeneration is a crucial process in returning muscle to its original function following damage. The accumulation of the extracellular matrix (ECM) is an important, yet often overlooked aspect during the regeneration process. With age, there is a decline in the regenerative capacity of skeletal muscle, partly attributed to the accumulation of the ECM, called fibrosis. Therefore, investigation into the contributors of fibrosis, namely plasminogen activator inhibitor-1 (PAI-1), is needed to better understand changes in the ECM during regeneration in aged muscle.

Methods: Young (3 month old) and aged (18 month old) male C57BL/6J mice were studied (n = 15). Muscle damage was induced via cardiotoxin (CTX) injection to the left tibialis anterior muscle. Mice were sacrificed at 3, 5 and 7 days following damage and muscles were collected. Immunohistochemical (IHC) techniques were used to investigate regenerative capacity, macrophage density, and macrophage-derived PAI-1 expression. A two-way ANOVA was used to determine statistical significance for the results.

Results: Myogenic potential of aged skeletal muscle was found to be significantly lower in the 7-day post-damage compared to young (main effect: p < 0.05). In addition, a significant increase in macrophage count at 7-day post-damage in aged skeletal muscle was observed. There was a significant difference in macrophage-derived PAI-1 content throughout the regeneration process between groups (p < 0.05). Discussion: Aged skeletal muscle was observed to have a diminished regenerative capacity as well as an increase in prolonged necrosis following damage. These findings suggest that the implications of macrophage-derived PAI-1 may have a negative effect on the ECM and the regenerative capacity of aged skeletal muscle.