The role of myostatin and activin receptor IIB in the regulation of unloading-induced myofiber type-specific skeletal muscle atrophy.

Abstract

Chronic unloading induces decrements in muscle size and strength. This adaptation is governed by a number of molecular factors including myostatin, a potent negative regulator of muscle mass. Myostatin must first be secreted into the circulation and then bind to the membrane-bound activin receptor IIB (actRIIB) to exert its atrophic action. Therefore, we hypothesized that myofiber type-specific atrophy observed after hindlimb suspension (HLS) would be related to myofiber type-specific expression of myostatin and/or actRIIB. Wistar rats underwent HLS for 10 days, after which the tibialis anterior was harvested for frozen cross sectioning. Simultaneous multichannel immunofluorescent staining combined with differential interference contrast imaging was employed to analyze myofiber type-specific expression of myostatin and actRIIB and myofiber type cross-sectional area (CSA) across fiber types, myonuclei, and satellite cells. Hindlimb suspension (HLS) induced significant myofiber type-specific atrophy in myosin heavy chain (MHC) IIx (P < 0.05) and MHC IIb myofibers (P < 0.05). Myostatin staining associated with myonuclei was less in HLS rats compared with controls, while satellite cell staining for myostatin remained unchanged. In contrast, the total number myonuclei and satellite cells per myofiber was reduced in HLS compared with ambulatory control rats (P < 0.01). Sarcoplasmic actRIIB staining differed between myofiber types (I < IIa < IIx < IIb) independent of loading conditions. Myofiber types exhibiting the greatest cytoplasmic staining of actRIIB corresponded to those exhibiting the greatest degree of atrophy following HLS. Our data suggest that differential expression of actRIIB may be responsible for myostatin-induced myofiber type-selective atrophy observed during chronic unloading.

• Authors: Lyle W Babcock, Mark Knoblauch, Mark S F Clarke
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 119 Issue 6 Pg. 633-42 (Sep 15 2015) ISSN: 1522-1601 [Electronic] United States
• PMID: 26205544 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Mstn protein, rat
• Myostatin
• Activin Receptors, Type II
• Myosin Heavy Chains

Topics

• Activin Receptors, Type II (metabolism)
• Animals
• Hindlimb Suspension (physiology)
• Male
• Muscle Fibers, Skeletal (metabolism)
• Muscle, Skeletal (metabolism)
• Muscular Atrophy (metabolism)
• Muscular Diseases (metabolism)
• Myosin Heavy Chains (metabolism)
• Myostatin (metabolism)
• Rats
• Rats, Wistar