Growth Arrest Specific 6 in Regeneration after Skeletal Muscle Injury

Abstract

Growth arrest‐specific 6 (Gas6) belongs to the family of vitamin K‐dependent proteins. Its functions in the cardiovascular, pulmonary and immune systems have been reported on in depth, but very little is known about its role in skeletal muscle. Because of its roles in the regulation of inflammation and cell proliferation in other tissues, our objective was to determine whether Gas6 plays an important role in skeletal muscle repair and/or regeneration after injury.Therefore, we unilaterally injured the tibialis anterior (TA) muscles of young adult (YA; 5 mo.) and old (O; 30 mo.) Fisher Brown‐Norway rats with barium chloride (n=5–8/group). At the time of injury we also implanted a subcutaneous osmotic pump that continuously infused Gas6 (4 mg/ml) or saline onto the TA muscle through silicone tubing. The contralateral muscles served as controls. One week after injury, blood and the TA muscles were collected and the rats were euthanized. Muscle sections were prepared and stained with hematoxylin and eosin. Muscle were homogenized and Gas6 concentration was measured by ELISA in both plasma and muscle homogenates.We found that muscle injury greatly increased Gas6 concentration in muscle, but not plasma. [Gas6] was greater in O vs. YA plasma, but age had no effect on Gas6 levels in skeletal muscle. Gas6 infusion increased regenerating muscle fiber size in YA rats, but not in O rats (n=3), despite a similar increase in Gas6 concentration with injury.These results suggest that Gas6 is likely an important player in the regeneration of skeletal muscle after injury, and that the impaired recovery of old skeletal muscle after injury may be due in part to Gas6 resistance.Support or Funding InformationResearch Support: BYU Gerontology Program GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.